Application of reagent for detecting MEOX1 in preparation of product for diagnosing Alport syndrome related diseases

Abstract

The invention provides application of a reagent for detecting MEOX1 in preparation of a product for diagnosing Alport syndrome related diseases, and relates to the technical field of tumors. According to the research of the inventor, the deletion of COL4A5 / COL4A6 gene fragments causes high expression of MEOX1 on basement membranes of multiple organ tissues of AS, so that the expression level of MEOX1 can be used for AS detection. In addition, the inventor researches and confirms that the bases of the kidney biopsy tissue and the esophageal lesion tissue of the AS-DL patient involve a common pathogenic mechanism of multiple visceral smooth muscles for AS-DL, which provides an important research clue for researching the common pathogenic mechanism of AS leiomyomatosis.

Description

Technical Field

[0001] The present invention relates to the field of tumor technology, and in particular to application of a reagent for detecting MEOX1 in preparing products for diagnosing Alport syndrome-related diseases. Background Art

[0002] Diffuse esophageal leiomyomatosis (DOL) is a rare disease associated with Alport syndrome (AS). It originates in the muscular layer of the esophageal wall, most commonly in the mid-esophageal segment, followed by the lower segment, and rarely in the cervical segment. Its pathological hallmark is diffuse hypertrophy of the esophageal muscular layer. AS-DOL typically develops in early childhood, with a median age of 3 years and generally younger than 13 years. DOL is often accompanied by clinical symptoms of digestive disorders, such as reflux, acid reflux, abdominal distension, and hematemesis. AS-DOL may cause intermittent dysphagia and pneumonia, often accompanied by dull pain in the chest, back, and upper abdomen. If the disease worsens, resulting in breathing and swallowing difficulties, thoracic surgery or even gastroesophageal anastomosis may be necessary.

[0003] AS-DOL is a rare extrarenal manifestation of Alport syndrome, occurring in approximately 5% of AS patients. AS is a rare inherited glomerular disease characterized by hematuria, progressive nephritis, sensorineural hearing loss, and ocular abnormalities. AS is primarily caused by mutations in the gene encoding type IV collagen in the glomerular basement membrane. Abnormal expression of type IV collagen leads to irregular thickening and thinning of the glomerular basement membrane, stratification and fragmentation of the lamina compacta, podocyte loss, glomerular sclerosis with extracellular matrix deposition, and renal fibrosis, ultimately leading to end-stage renal disease. Literature reports suggest that diffuse leiomyomatosis in AS can affect the gastroesophageal tract, trachea, and female reproductive tract (such as the clitoris, labia majora, and uterus). Pathological changes in the esophagus are particularly common in all patients, and the earliest clinical manifestation in this population is upper gastrointestinal symptoms such as dysphagia caused by esophageal tumors.

[0004] The diagnosis, treatment, and prognosis of diffuse leiomyomatosis (AS) have always been a challenge for pediatricians. Clarifying the pathogenesis of diffuse esophageal muscular hyperplasia (DHL) is a crucial prerequisite for prevention and treatment. Despite the low incidence of AS-DOL, research on this condition is limited both domestically and internationally.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The first object of the present invention is to provide a reagent for detecting MEOX1 for use in preparing a product for diagnosing Alport syndrome-related diseases, so as to solve the above technical problems.

[0007] The second object of the present invention is to provide a kit for diagnosing Alport syndrome-related diseases.

[0008] The third object of the present invention is to provide use of a drug targeting MEOX1 in the preparation of a drug for treating Alport syndrome-related diseases.

[0009] In order to achieve the above objectives, the following technical solutions are adopted: In a first aspect, the present invention provides use of a reagent for detecting MEOX1 in the preparation of a product for diagnosing Alport syndrome-related diseases.

[0010] As a further technical solution, the Alport syndrome-related diseases include Alport syndrome-diffuse leiomyomatosis (AS-DL); The Alport syndrome-diffuse leiomyomatosis includes Alport syndrome-diffuse esophageal leiomyomatosis.

[0011] As a further technical solution, the samples detected by the reagent include kidney tissue and esophageal lesion tissue.

[0012] As a further technical solution, the MEOX1 is upregulated in the basement membrane of the kidney tissue and the basement membrane of the esophageal tissue of patients with Alport syndrome-diffuse leiomyomatosis.

[0013] As a further technical solution, the product includes a kit.

[0014] In a second aspect, the present invention provides a kit for diagnosing Alport syndrome-related diseases, comprising primers for detecting MEOX1 mRNA or a marker for labeling MEOX1 protein.

[0015] As a further technical solution, the primers are used to detect the expression level of MEOX1 by PCR.

[0016] As a further technical solution, the marker includes an antibody for specifically recognizing MEOX1 protein.

[0017] In a third aspect, the present invention provides the use of a drug targeting MEOX1 in the preparation of a drug for treating Alport syndrome-related diseases.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The inventors' research has found that deletion of the COL4A5 / COL4A6 gene fragment leads to high expression of MEOX1 in the basement membranes of multiple organs and tissues in AS. Therefore, MEOX1 expression levels can be used to detect AS. Furthermore, the inventors' research has confirmed that the basement membranes of renal biopsies and esophageal lesions in AS-DL patients share a common pathogenic mechanism of AS-DL affecting smooth muscle in multiple organs, providing important research clues for studying the common pathogenic mechanisms of AS leiomyomatosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0020] Figure 1 Esophageal tissue and whole-exome sequencing for Alport syndrome-diffuse esophageal leiomyomatosis; Figure 2 A single-cell transcriptomic map of the pathological process of AS-DOL esophageal tumors; Figure 3 To analyze the cell differentiation trajectory of esophageal basal stem cells; Figure 4 To analyze the functional characteristics of the differentiation trajectory of esophageal basal stem cells using single-cell transcriptomics; Figure 5 MEOX1 is highly expressed in the esophageal basement membrane tissue of Alport syndrome-esophageal leiomyomatosis; as the AS-DL esophagus transitions from normal tissue to diseased tissue, MEOX1 expression increases. Figure 6 MEOX1 is highly expressed in renal endothelial cells of patients with Alport syndrome (AS). DETAILED DESCRIPTION

[0021] Below in conjunction with embodiment and example, embodiment of the present invention is described in detail, but those skilled in the art will appreciate that the following embodiment and example are only used to illustrate the present invention, and should not be considered as limiting the scope of the present invention. Based on the embodiment in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work premise all fall within the scope of protection of the present invention. Unspecified conditions are carried out according to the conditions of normal conditions or manufacturer's recommendations. Reagents used or instruments not specified by the manufacturer are conventional products that can be purchased commercially.

[0022] In a first aspect, the present invention provides use of a reagent for detecting MEOX1 in the preparation of a product for diagnosing Alport syndrome-related diseases.

[0023] The inventors have found that the deletion of COL4A5 / COL4A6 gene fragments leads to high expression of MEOX1 in the basement membranes of multiple organs and tissues in AS. Therefore, the expression level of MEOX1 can be used to detect AS.

[0024] In the present invention, the Alport syndrome-related diseases include Alport syndrome, Alport syndrome-diffuse leiomyomatosis; The Alport syndrome-diffuse leiomyomatosis includes Alport syndrome-diffuse esophageal leiomyomatosis.

[0025] In some optional embodiments, the samples detected by the reagent include kidney tissue and esophageal lesion tissue.

[0026] The expression of MEOX1 is upregulated in the basement membrane of renal tissue and esophageal tissue of patients with Alport syndrome-diffuse leiomyomatosis.

[0027] In some alternative embodiments, the product comprises a kit.

[0028] In a second aspect, the present invention provides a kit for diagnosing Alport syndrome-related diseases, comprising primers for detecting MEOX1 mRNA or a marker for labeling MEOX1 protein.

[0029] This kit detects MEOX1 to diagnose Alport syndrome-related diseases.

[0030] In some optional embodiments, the primers are used to detect the expression level of MEOX1 by PCR.

[0031] In some optional embodiments, the marker includes an antibody for specifically recognizing MEOX1 protein.

[0032] In a third aspect, the present invention provides the use of a drug targeting MEOX1 in the preparation of a drug for treating Alport syndrome-related diseases.

[0033] The present invention is further described below by way of specific examples. However, it should be understood that these examples are merely provided for more detailed description and are not to be construed as limiting the present invention in any form.

[0034] Example 1 1. Clinical specimen collection: Clinical information was collected from two families diagnosed with Alport syndrome-diffuse esophageal leiomyomatosis (AS-DOL) at our hospital between 2014 and 2024, including age, sex, symptoms, medical history, and major positive test results. Blood samples were collected from children with AS and AS-DOL, their parents, and siblings for genetic screening. DNA was extracted from 4 mL of peripheral blood and stored at -20°C. Esophageal tissue specimens obtained during surgery were frozen at -80°C and prepared as paraffin-embedded specimens. Informed consent was obtained from the patients' families, and specimens were obtained in strict accordance with the approval procedures of the institutional ethics committee.

[0035] 2. Whole-exome sequencing: Whole-exome sequencing was performed on blood samples from children with AS and AS-DOL, their parents, and siblings. High-quality variants were prioritized using the following steps: (1) variants within intergenic, intronic, and untranslated regions (UTRs), as well as synonymous mutations, were excluded from downstream analysis; (2) variants with a quality score below 20 were excluded using software screening; (3) a phyloP score above 3 was obtained based on comparisons of humans and vertebrates using public databases; and (4) the potential effects of the variants were predicted using PolyPhen-2 software (http: / / genetics.bwh.harvard.edu / pph2 / ). The final selected variants were screened using a comprehensive genome browser, and previously described polymorphic variants in public data were investigated and matched to variants found in the proband's exome. DNA from the patient and family members was PCR amplified, primers were designed using online tools, and the mutated gene was verified by Sanger sequencing.

[0036] Whole-exome sequencing and copy number variation analysis of blood samples from two children with AS-DOL in our hospital showed that one patient had a copy number deletion of approximately 307Kb on the long arm of chromosome Xq22.3 (chrX:g.107629348_107936348del), and the other patient had a copy number deletion of approximately 40Kb on the long arm of chromosome Xq22.3 (chrX:g.107645023_107685353del). Whole-exome sequencing of blood samples from both children involved deletions of two long fragments of the collagen IV chain COL4A5 / COL4A6 gene.

[0037] 3. Single-cell transcriptomic mapping of the pathological process of AS-DOL esophageal tumors based on single-cell sequencing: Based on preoperative imaging data, the esophageal lesions in AS-DOL patients can be divided into the upper esophageal segment (normal site), middle segment (transitional site), and lower segment (thickened site). Fresh esophageal tissue specimens obtained during surgery were subjected to 10× single-cell sequencing (scRNA-seq) to generate single-cell transcriptomic maps and identify and annotate individual cell types.

[0038] 4. Process of single-cell preparation and sequencing technology for esophageal tissue: 1) Cell Quality Assay: Esophageal tissue from AS-DOL (one sample each from the upper, middle, and lower esophagus) was isolated and lysed using a flow cytometer to prepare a cell suspension. Cells were counted using a Countess® II Automated Cell Counter and adjusted to the desired concentration (generally no less than 1000 cells / μL) with cell viability greater than 90%. 2) Labeling cDNA fragments: Gel beads containing barcode information are bound to a mixture of cells and enzymes and then encapsulated by oil-surfactant droplets within a microfluidic "double-cross" system, forming GEL BEADS-IN-EMULSIONS (GEMs). The GEMs flow into a reservoir and are collected. The gel beads dissolve, releasing the barcode sequence. The cDNA fragments are reverse transcribed and labeled. The gel beads are then broken up, disrupting the oil droplets. PCR amplification is performed using the cDNA as a template. Products from all GEMs are pooled to construct a standard sequencing library. 3) Library Construction and Sequencing: First, the cDNA was ultrasonically fragmented into fragments of approximately 200-300 bp. Sequencing adapter P5 and primer R1 were added, following the traditional next-generation sequencing library construction process. Finally, PCR amplification was performed to generate a DNA library. The constructed library was subjected to high-throughput sequencing using the paired-end sequencing mode of the Illumina sequencing platform. 4) Data Quality Control: Data quality statistics were analyzed using the 10× configuration analysis software Cell Ranger, which was used to analyze the raw data and compare them to the reference genome. This software quantifies high-throughput single-cell transcriptomes by identifying barcode sequence tags (to distinguish cells) and UMI (Unique Molecular Identifier) ​​tags (to distinguish different mRNA molecules within each cell).

[0039] 5) Differential Expression Analysis and Mapping: Seurat's bimodal likelihood ratio test was used to screen for specific differentially expressed genes in different cell populations. Using an FDR <= 0.01 and a differential expression factor >= 2 as screening criteria, differentially expressed genes were identified between a specific cell population and the rest. Important cell populations, key regulatory transcription factors, and chromatin accessibility peak motifs were identified through marker gene screening and regulatory network analysis.

[0040] 5. Integrating single-cell transcriptomics (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) To improve the accuracy and cellular resolution of scATAC-seq data, scRNA-seq data clustering and annotation were mapped to scATAC-seq cell clusters. Based on the principle of similarity, scRNA-seq data were used to identify scATAC-seq cell clusters. By combining two omics datasets—SECNIC results from scRNA-seq and ChromVAR results from scATAC-seq—the intersection of these two datasets revealed the true expression of core regulatory transcription factors.

[0041] 6. AS-DOL is associated with deletions of the COL4A5 / COL4A6 gene fragment on chromosome X. In the early stages of this study, whole-genome screening of families with AS-DOL in our hospital revealed characteristic deletions of long fragments of the COL4A5 / COL4A6 gene, particularly deletions of the 4.2 kb critical region ( Figure 1 The deletion of this gene fragment involves intron 2 of COL4A6 to intron 1 of COL4A5, and even includes the entire COL4A5 gene. The gene deletion in this region may prevent the biosynthesis of type IV collagen, but the specific regulatory mechanism remains unclear.

[0042] Figure 1In this study, (A) Gross morphology of AS-DOL esophageal mass and CT images of esophagus before and after surgery. According to the location of AS-DOL lesions, it can be divided into upper segment (normal site), middle segment (transition site) and lower segment (thickening site) of esophagus. It can be seen that the esophageal tissue near the gastric cardia in the lower segment of the esophagus has obvious diffuse hyperplasia and hypertrophy. The esophageal mass gradually extends from the lower segment to the upper segment of the esophagus. (B) Two cases of AS-DOL children in our hospital were analyzed by blood sample whole exome sequencing and copy number variation. The results showed that: 1 case of X chromosome long arm Xq22.3 had a copy number deletion of about 307Kb (chrX:g.107629348_107936348del), and another case of X chromosome long arm Xq22.3 had a copy number deletion of about 40Kb (chrX:g.107645023_107685353del); The whole exome detection of 2 cases of children involved the deletion of long fragments of two collagen IV chains COL4A5 / COL4A6 genes (horizontal dashed line). (C) Summarize the literature AS and AS diffuse leiomyomatosis (AS-DL) family case reports (the numbers in the figure are case numbers), there is a characteristic deletion of COL4A5 / COL4A6 gene fragments, especially the 4.2 kb key deletion region (red font, vertical dashed line).

[0043] 7. To explore the common pathogenic mechanism of AS-DOL involving multiple organs smooth muscle, typical esophageal lower segment lesion tissue and esophageal upper segment tissue (normal tissue) of the same patient were selected for scRNA-seq and scATAC-seq analysis, the results showed that esophageal basal stem cells with stem cell characteristics played a key role in the pathological changes of AS-DOL esophagus. Figure 2 and Figure 3 ).

[0044] Figure 2Single-cell transcriptomic atlas of AS-DOL esophageal mass lesion process was demonstrated. (A) According to the imaging data, the esophageal mass lesion site was divided into upper, middle and lower esophagus, among which the lower esophagus was the site of leiomyoma formation. The imaging data showed that the lower esophagus was significantly thickened and enlarged. The transcriptome data set of 28331 cells was obtained by 10x single-cell sequencing, with an average of 9000 cells per sample. The cell clusters were annotated by the expression of typical marker genes. By dimensionality reduction clustering (UMAP), the esophageal mass was divided into 9 major cell lineages, namely endothelial cells, epithelial cells, fibroblasts, mast cells, monocytes, neutrophils, pericytes, Schwann cells and T cells. The column chart shows that when the lower esophagus develops leiomyoma pathological changes, the proportion of esophageal epithelial cells increases significantly, suggesting that esophageal epithelial cells may be an important cell type leading to AS-DOL. (B) Different types of cells were analyzed by UMAP clustering analysis to draw a single-cell transcriptomic atlas. Esophageal epithelial cells were selected as the focus of the study (red dotted line). (C) Distribution of different types of cells in different esophageal sites, among which esophageal epithelial cells mainly distributed in the lower esophagus.

[0045] Figure 3 To analyze the cell differentiation trajectory of esophageal basal stem cells. (A) Four subpopulations of esophageal epithelial cells were identified by dimensionality reduction analysis and typical marker genes, and esophageal basal stem cells were screened (dotted line area). Further single-cell atlas analysis showed that esophageal basal stem cells significantly highly expressed 10 genes, including DST, COL17A1, CDH3, IL1R2, TNC, LAMC2, MIR205HG, P3H2, DST and KRT15. (B) Cell differentiation trajectory analysis was performed according to the stemness of the four subpopulations of esophageal epithelial cells, showing a semicircular trajectory, with the differentiation order being esophageal basal stem cells (blue), esophageal proliferative basal cells (green), esophageal basal suprabasal cells (purple) and esophageal parabasal cells (red) in turn. The results showed that esophageal basal stem cells were located at the starting position of the cell differentiation main stem, further suggesting that esophageal epithelial cells originated from esophageal basal stem cells. (C) Cell differentiation trajectory of each of the four subpopulations of esophageal epithelial cells. (D) Esophageal basal stem cells (light blue) mainly distributed in the lower esophagus (red area) of AS-DOL lesion site, suggesting that esophageal basal stem cells may have important effects on the pathological formation process of AS-DOL esophageal mass.

[0046] Using the single-cell transcription factor analysis tool SCENIC, we further constructed the transcription factor and target gene regulatory network (regulons) of the four cell subpopulations of esophageal epithelial cells. The Regulons activity heat map based on the AUC value showed that there was obvious heterogeneity in Regulons activity among these four cell subpopulations. Among them, esophageal basal stem cells highly expressed transcription factors such as NFKB1, MEOX1, IRF1, NFATC1, SOX4, RFX2, SOX6, GATA6, and SOX5. Among them, MEOX1 is a transcription factor specifically expressed by esophageal basal stem cells ( Figure 4 ).

[0047] Figure 4 Single-cell transcriptomics analysis of the functional characteristics of the differentiation trajectory of esophageal basal stem cells. (A) Pseudo-time series analysis of the differentiation trajectory of esophageal basal stem cells revealed that esophageal basal stem cells (blue) are located at the initiation site of the main differentiation trunk. (B) Comparison of highly expressed functionally differentially expressed genes among four types of esophageal basal stem cells (blue), esophageal proliferating basal cells (green), esophageal suprabasal cells (purple), and esophageal parabasal cells (red). Signaling pathways in esophageal basal stem cells were analyzed using the QuSAGE algorithm. KEGG enrichment analysis results for highly expressed differentially expressed genes are displayed in bubble plots. These genes primarily involve the extracellular matrix-receptor interation pathway, focal adhesion pathway, ferroptosis pathway, Hippo signaling pathway, EGFR signaling pathway, TNF signaling pathway, and Th17 cell differentiation regulatory pathway. (C) A heat map of Regulons openness drawn based on the AUC binary matrix shows open Regulons among the four cell subsets of esophageal epithelial cells, among which esophageal basal stem cells highly express transcription factors such as NFKB1, MEOX1, IRF1, NFATC1, SOX4, RFX2, SOX6, GATA6, and SOX5.

[0048] Combine Figure 2 and Figure 3 、 Figure 4 Further research revealed that MEOX1 is a highly expressed transcriptional gene specifically in esophageal basal stem cells. MEOX1 triggers pathological changes in AS-DL esophageal tissue by activating the Hippo / YAP signaling pathway. MEOX1 is a human homologous gene that regulates cell growth and differentiation potential. It binds to specific genomic DNA motifs to regulate the expression of target genes and is closely associated with bone, vascular, and muscle development.

[0049] 8. MEOX1, which is specifically expressed in esophageal basal stem cells, and the COL4A5 / COL4A6 gene deletion region, have transcriptional binding sites for the key transcription factor motify. Combined scRNA-seq and scATAC-seq analyses of esophageal basal stem cell transcriptional gene expression and open chromatin profiles were performed. JASPAR website was used to predict the transcriptional binding sites of key candidate transcription factors within the 4.2 kb critical deletion region of the COL4A5 / COL4A6 gene fragment. This further confirmed the presence of TF motify transcriptional binding sites for MEOX1 within the COL4A5 / COL4A6 gene deletion region.

[0050] Immunohistochemical staining of esophageal samples from two other AS-DOL children showed that MEOX1 was mainly distributed in the basement membrane of the esophageal tissue, and as the AS-DOL esophagus transitioned from normal tissue to diseased tissue, MEOX1 expression increased ( Figure 5 ), which suggests that MEOX1 may serve as a potential therapeutic target for AS-DL.

[0051] 9. Immunohistochemical analysis was performed on renal biopsy specimens from 10 children with Alport syndrome (experimental group) and 2 children with nephritic syndrome (control group). Figure 6 The results showed that MEOX1 (arrow) was highly expressed mainly in the basement membrane region of renal endothelial cells, whereas MEOX1 expression was significantly reduced in renal tissues of nephritic syndrome, suggesting that there was spatial consistency between the abnormal basement membranes of multiple organs in AS patients and the MEOX1 expression pattern.

[0052] 10. Loss of the COL4A5 / COL4A6 gene fragment may lead to high expression of MEOX1 in the basement membranes of multiple organs and tissues in AS-DL. Previous studies have shown that esophageal basal stem cells specifically expressing MEOX1 are located in the esophageal basement membrane. AS patients exhibit pathological changes such as vascular and cardiac abnormalities, as well as thickening, atrophy, and interstitial fibrosis of the renal tubular basement membrane. These changes are associated with basement membrane structural instability caused by defects in the type IV collagen network. MEOX1 is a human homologous gene located on chromosome 17q21.31 that regulates cell growth and differentiation potential. It encodes 254 amino acids and has three isoforms. Studies have found that MEOX1 is specifically highly expressed in nephron progenitor cells during the developmental trajectory of human embryonic metanephrocytes. Studies have reported that MEOX1 is a transcription factor that plays a key role in the differentiation of fibroblasts into myofibroblasts. MEOX1 can mediate TGF-β-induced nuclear retention of Smad3, inducing the differentiation of mouse mesenchymal progenitor cells into smooth muscle cells. Previous immunohistochemical results confirmed that the basement membranes of AS-DL patients' renal biopsies and esophageal lesions highly express MEOX1, providing new theoretical support for the shared pathogenic mechanism of AS-DL affecting smooth muscle across multiple organs. This suggests that high expression of MEOX1 in the basement membrane is highly correlated with the common pathological changes in multiple tissues. This study, focusing on typical esophageal smooth muscle pathological changes, will provide important insights into the shared pathogenic mechanisms of AS-DL and leiomyomatosis.

[0053] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. Application of reagents for detecting MEOX1 in the preparation of products for diagnosing Alport syndrome-related diseases.

2. The use according to claim 1, characterized in that The Alport syndrome-related diseases include Alport syndrome-diffuse leiomyomatosis; The Alport syndrome-diffuse leiomyomatosis includes Alport syndrome-diffuse esophageal leiomyomatosis.

3. The use according to claim 1, characterized in that The samples detected by the reagent include kidney tissue and esophageal lesion tissue.

4. The use according to claim 1, characterized in that The expression of MEOX1 is upregulated in the basement membrane of renal tissue and esophageal tissue of patients with Alport syndrome-diffuse leiomyomatosis.

5. The use according to claim 1, characterized in that The products include kits.

6. A kit for diagnosing Alport syndrome-related diseases, characterized in that: The method includes primers for detecting MEOX1 mRNA or markers for labeling MEOX1 protein.

7. The kit according to claim 6, characterized in that The primers are used to detect the expression level of MEOX1 by PCR.

8. The kit according to claim 6, characterized in that The marker includes an antibody for specifically recognizing MEOX1 protein.

9. The application of drugs targeting MEOX1 in the preparation of drugs for the treatment of Alport syndrome-related diseases.

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