| First Author | Maydan O | Year | 2018 |
| Journal | Physiol Rep | Volume | 6 |
| Issue | 6 | Pages | e13654 |
| PubMed ID | 29595914 | Mgi Jnum | J:312340 |
| Mgi Id | MGI:6781028 | Doi | 10.14814/phy2.13654 |
| Citation | Maydan O, et al. (2018) Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy. Physiol Rep 6(6):e13654 |
| abstractText | Human GWAS and Mendelian genetic studies have linked polymorphic variants and mutations in the human uromodulin gene (UMOD) with chronic kidney disease. The primary function of this kidney-specific and secreted protein remains elusive. This study investigated whether UMOD deficiency modified responses to unilateral ureteral obstruction (UUO)-induced kidney injury. Kidneys harvested from groups of wild-type (UMOD+/+) and knockout (UMOD-/-) male mice (n = 7-10 each) were studied on days 7, 14, and 21. Compared to sham kidneys, UMOD protein levels increased 9-13x after UUO and were associated with increased urinary UMOD levels. Kidney KIM-1 protein levels were higher in the UMOD-/- groups at all time-points (4-14x). The UMOD-/- groups also had higher KIM-1 kidney-to-urine relative ratios (5-35x). In vitro studies using KIM-1 expressing 769-P cells showed lower KIM-1 levels in the presence of UMOD protein. Levels of proapoptotic genes and the epithelial cell apoptotic protein marker M30 were significantly lower in the UMOD-/- groups. Both M30 and KIM-1 colocalized with intraluminal UMOD protein deposits. Interstitial inflammation was less intense in the UMOD-/- groups. Renal fibrosis severity (kidney collagen mRNA and protein) was similar in both genotypic groups on days 7, 14, and 21. Our findings suggest a role for UMOD-dependent inhibition of KIM-1 expression and its apoptotic cell scavenging responses during chronic obstruction-associated tubular injury. |
