FP302HYPOXIA INDUCEDHE4 IN TUBULAR EPITHELIAL CELLS PROMOTES THE ACCUMULATION OF ECM AND RENAL FIBROSIS THROUGH NF- κB SIGNALS
Year: 2018
Type: conference-abstract
Abstract: INTRODUCTION AND AIMS: Hypoxia-induced extracellular matrix (ECM) deposition is an important cause of renal fibrosis. The mechanism of hypoxia triggering ECM deposition is unclear. HE4 is a newly discovered key molecule that can cause ECM deposition. But the mechanism still remains largely unknown. This study was to determin the uncovering a novel function and molecular mechanism for HE4 in hypoxia-induced ECM deposition in renal fibrosis. METHODS: Western blot and quantitative Real-Time PCR were used to examine the expression of HE4 in HK2 cells induced by hypoxia and UUO models. HE4 binding site was analysed by dual-luciferase reporter gene assay and chromatin immunoprecipitation assay. The abundance of HE4 was measured by ELISA in the serum of patients with CKD. Therole of HE4 in vivo was explored with lentivirus injection in C57 mice with UUO. RESULTS: HE4 was significantly increased in renal tubular epithelial cells induced by hypoxia and UUO models. In addition, overexpression of HE4 can activate NF-κB pathway to upregulate TIMP1 which could inhibit degradation of ECM by inhibiting the activity of MMP2. In vivo, with a Lv-HE4 treat the C57 mice before UUO could reverse the fibrosis. Meanwhile, the expression of HE4 proteins in the tubulointerstitiumwas positively correlated with the percentage of tubulointerstitial fibrosis in renal tissue samples and serum from chronic kidney disease patients. CONCLUSIONS: Our findings provide mechanistic insight into hypoxia induction renal fibrosis via up-regulation of HE4, which could increase the accumulation of ECM through NF-κB signal pathway. Uncovering a novel function and molecular mechanism for HE4 overexpression in hypoxia-induced renal fibrosis provides important insight into understanding renal fibrosis and antifbrogenesis strategies .
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2804773765