Uromodulin Alleviates Interstitial Fibrosis in AKI to CKD Transition in a Cisplatin-Treated Rat Model via the Inhibition of EGFR Pathway
- AKI: Mechanisms - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
- Xing, Zheyu, Peking University First Hospital Department of Nephrology, Beijing, China
- Chen, Yuqing, Peking University First Hospital Department of Nephrology, Beijing, China
Severe or recurrent acute kidney injury (AKI) episode is liable to cause the occurrence and acceleration of chronic kidney disease (CKD). Uromodulin has been reported as a protective factor for AKI and CKD. Here, we explored its role in the AKI-CKD transition.
Wild-type SD rats and UMOD-/- rats were given cisplatin at 3.2mg/kg for 4 times every 2 weeks to induce the transition of AKI-CKD. Serum, urine and kidneys were collected to assay the protect effect of uromodulin. Western blots, IHC and qPCR were used to investigate mechanisms. HK-2 cell culture in cisplatin was treated with or without uromodulin for further validation.
UMOD-/- rats didn’t develop spontaneous kidney injury or fibrosis. However, uromodulin deficiency accelerated the progression of AKI to CKD in our rat model, as evidenced by more serious kidney insufficiency and fibrosis. The levels of SCR, BUN, urinary KIM1 and NGAL were significantly increased in cisplatin-treated UMOD-/- rats compared with UMOD+/+ rats. PAS and Sirius staining showed heavier renal lesion and fibrosis in UMOD-/- rats. During the transition of AKI-CKD, UMOD-/- rats showed elevated levels of fibrosis markers and over-activation of EGFR/ERK, according to Western blot and IHC. The native uromodulin supplement to cisplatin-stimulated HK-2 cells decreased the expressions of fibroblast markers and down-regulated the EGFR/EKR.
Uromodulin deficiency may exacerbate the progression of AKI-CKD transition induced by cisplatin via the overactivation of EGFR.
- Government Support – Non-U.S.