대한신장학회

논문분류	춘계학술대회 초록집
제목	Proximal tubule-specific deletion of Sirt1 aggravates renal fibrosis in unilateral ureteral obstruction model.
저자	JIHYUN YEOM
출판정보	2023; 2023(1):
키워드
초록	Objectives: The epithelial-to-mesenchymal transition (EMT) of tubular cells is a complex process in which damaged epithelial cells acquire mesenchymal cell characteristics, contributing to renal fibrosis in different kidney disease models. Sirtuins are nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases essential in various renal diseases such as acute/chronic kidney injury, diabetic kidney disease, and inflammation. We aimed to elucidate the role of proximal tubular Sirt1 in renal fibrosis induced by unilateral ureteral obstruction. Methods: To investigate the specific role of tubular SIRT1 in unilateral ureteral obstruction (UUO)-induced renal fibrosis, tubule-specific Sirt1 conditional knockout (KO) mice and their control littermates were generated. The kidney sample was harvested 1 week after UUO. Results: We screened homozygous Sirt1-floxed mice (Sirt1flox/flox) with or without Cre (gGT-Cre) transgene expression by quantitative real-time PCR (qRT-PCR) using laser capture microdissection. Proximal tubular cells were stained by lectin and then isolated by attaching the tissue to the laser capture microdissection. Tubule-specific Sirt1 KO mice and their control littermates had a normal appearance and no difference in the size or morphology of the kidney. Periodic acid Schiff (PAS) staining demonstrates an increased kidney injury score elicited by UUO in Sirt1 KO mice. Fibrotic area after staining with MTS, Sirus red was significantly higher in the kidney of Sirt1 KO mice than that of wild-type mice. In addition, there was increased protein expression of fibronectin and collagen type 1 in the UUO kidney, performed with immunoblot. Kidney tubule cell-specific deletion of Sirt1 increased smooth muscle actin and vimentin expression but decreased E-cadherin expression in kidney proximal tubular epithelial cells. We observed a dramatic upregulation of the protein expression of ICAM-1 and infiltration of F4/80 or FSP1-positive cells in the UUO kidney of the Sirt1 KO mouse. Conclusions: Collectively, our findings suggest that the proximal tubule-specific deletion of Sirt1 ameliorates renal fibrosis in the unilateral ureteral obstruction model.
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