Methods for assessing megalin expression and function in human tissues

Abstract

The present invention is a method for evaluating megalin expression level or megalin ligand reabsorption capability of megalin, the method including a step in which: 1) when the megalin concentration in urine or cerebral spinal fluid derived from a test subject decreases, it is evaluated that megalin expression is suppressed in the test subject and / or the megalin ligand reabsorption capability of megalin has been declined; and 2) when the megalin concentration in urine or cerebral spinal fluid derived from a test subject increases, it is evaluated that megalin expression is promoted in the test subject and / or the megalin ligand reabsorption capability of megalin has been increased.

Claims

1. A method for evaluating the expression level of megalin or the resorption function of megalin ligand by megalin, comprising the steps of: 1) When the concentration of megalin in the urine or cerebrospinal fluid from a subject is decreased, it is evaluated that the expression of megalin in the subject is suppressed and / or the reabsorption function of megalin ligand by megalin is decreased; 2) evaluating whether expression of megalin in a subject is enhanced and / or whether the reabsorption function of megalin ligand by megalin is increased when the concentration of megalin in urine or cerebrospinal fluid from the subject is increased.

2. The method of claim 1, wherein the concentration of megalin is 1) full-length human megalin, which is a full-length human megalin consisting of amino acids 26 to 4655 of the amino acid sequence shown in Sequence Table 1, or 2) a human megalin extracellular domain fragment lacking the intracellular domain and transmembrane domain, which is a human megalin extracellular domain fragment consisting of all or part of the amino acid sequence from amino acids 26 to 4363 of SEQ ID NO:

1.

3. The method according to claim 1 or 2, wherein the megalin whose expression or resorption function is evaluated is present on the cell membrane of the luminal side of the proximal tubule epithelial cell.

4. The method according to any one of claims 1 to 3, wherein the subject is being treated with a drug having an inhibitory effect on the expression of human megalin protein.

5. The method according to claim 4, wherein the drug is an SGLT2 (sodium glucose cotransporter 2) inhibitor.

6. The method according to claim 4 or 5, wherein the evaluation step is carried out by comparison with the megalin concentration in urine or cerebrospinal fluid before treatment.

7. The method according to any one of claims 1 to 6, wherein the concentration of human megalin in urine is a creatinine-corrected concentration of human megalin in urine (picomol of human megalin / gram of creatinine) obtained by dividing the concentration of human megalin quantified in urine by the concentration of creatinine in urine.

8. The method according to claim 7, wherein the threshold for the creatinine-corrected concentration of full-length megalin is 0.524 or less, and the normal range is below the threshold.

9. The method described in claim 7, wherein the threshold of the creatinine-corrected concentration of a human megalin extracellular domain fragment lacking the intracellular domain and transmembrane domain and consisting of all or part of the amino acid sequence from amino acid 26 to amino acid 4363 of SEQ ID NO: 1 is 211 or less, and a value below the threshold is considered to be in the normal range.

10. The method according to any one of claims 1 to 8, wherein the subject suffers from one or more diseases selected from the group consisting of diabetes, kidney disease, and diseases of the central nervous system.

11. A diagnostic marker for evaluating the expression level of megalin or the resorption function of megalin ligand by megalin, 1) A full-length human megalin consisting of the 26th to 4655th amino acids of the amino acid sequence shown in Sequence Listing 1; or 2) A diagnostic marker consisting of a human megalin extracellular domain fragment lacking the intracellular domain and transmembrane domain, which fragment consists of all or part of the amino acid sequence from amino acid 26 to amino acid 4363 of SEQ ID NO:1.

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