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Application of human epididymal protein 4 in preparation of NF-[kappa]B agonist

A human epididymis protein and agonist technology, applied in the field of biomedicine, can solve problems such as molecular mechanisms that have not yet been elucidated

Active Publication Date: 2018-06-15
FOURTH MILITARY MEDICAL UNIVERSITY
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Problems solved by technology

Our previous research found that hypoxia can cause ECM, especially collagen deposition, and participate in renal fibrosis, but its molecular mechanism has not yet been elucidated

Method used

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  • Application of human epididymal protein 4 in preparation of NF-[kappa]B agonist
  • Application of human epididymal protein 4 in preparation of NF-[kappa]B agonist
  • Application of human epididymal protein 4 in preparation of NF-[kappa]B agonist

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Embodiment 1

[0019] 1. Materials and methods

[0020] 1. Cell culture and experimental conditions The human proximal renal tubular epithelial cell line (HK2) was cultured in F12 medium (Invitrogen, Carlsbad, CA) with 10% fetal bovine serum. Under normal conditions (21%O 2 ,5%CO 2 ,37℃) and hypoxia (1%O 2 , 5% CO 2 , 37°C) incubator (Precision Scientific, Winchester, VA, USA) for 0, 6, 12, 24, 48 and 72 hours of cultivation.

[0021] 2. Animal model C57BL / 6J mice, male, weighing 20-30 g, were purchased from the Experimental Animal Center of Air Force Military Medical University (Xi'an, China). The UUO model was constructed by blocking the left ureter, and the animals were sacrificed 1 week, 2 weeks, and 3 weeks later, and samples were taken immediately, part of which was fixed with 4% paraformaldehyde, and the other part was stored at -80°C for analysis. All mouse work was performed in accordance with the guidelines of the Animal Care and Ethics Committee of the Experimental Animal Cen...

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Abstract

The invention discloses an application of a human epididymal protein 4 in preparation of an NF-[kappa]B agonist. Hypoxia is suggested to be able to induce high expression of renal tubular epithelial cell endogenous HE4. Highly-expressed HE4 induces activation of an NF-[kappa]b pathway to further up-regulate a downstream molecule TIMP1 of NF-[kappa]b so as to promote renal fibrosis. The discovery provides an important enlightenment on the renal fibrosis mechanism and anti-fibrosis treatment.

Description

Technical field: [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of human epididymis protein 4 (HE4) protein in the preparation of NF-κB agonist. Background technique: [0002] Renal interstitial fibrosis is an abnormal injury repair response caused by various CKDs. The main pathological manifestation is the network scar structure formed by the proliferation of myofibroblasts and the deposition of a large amount of extracellular matrix (ECM), which is the manifestation of excessive repair. . Renal fibrosis is a common pathological manifestation in the progression to end-stage of many chronic kidney diseases [1], which is mainly characterized by ECM thickening, preceded by inflammation or tissue damage [2]. ECM is an important part of tissue structure and organ remodeling, containing important structural proteins (such as collagens, fibronectin and laminins), which are important for the occurrence and development of fibr...

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Application Information

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IPC IPC(8): A61K38/17A61P13/12C12Q1/6851
CPCA61K38/1709C12Q1/6851C12Q2531/113C12Q2521/107
Inventor 刘利敏孙世仁杜锐吴垚张磊柳敏娜柏明李东刘宝建
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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