Susceptibility of renal fibrosis in diabetes: Role of hypoxia inducible factor-1.

Autor: Mei S; Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai, China.; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia, USA., Li L; Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai, China., Zhou X; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China., Xue C; Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai, China., Livingston MJ; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia, USA., Wei Q; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia, USA., Dai B; Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai, China., Mao Z; Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai, China., Mei C; Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai, China., Dong Z; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2022 Aug; Vol. 36 (8), pp. e22477.
DOI: 10.1096/fj.202200845R
Abstrakt: Diabetes may prevent kidney repair and sensitize the kidney to fibrosis or scar formation. To test this possibility, we examined renal fibrosis induced by unilateral ureteral obstruction (UUO) in diabetic mouse models. Indeed, UUO induced significantly more renal fibrosis in both Akita and STZ-induced diabetic mice than in nondiabetic mice. The diabetic mice also had more apoptosis and interstitial macrophage infiltration during UUO. In vitro, hypoxia induced higher expression of the fibrosis marker protein fibronectin in high glucose-conditioned renal tubular cells than in normal glucose cells. Mechanistically, hypoxia induced significantly more hypoxia-inducible factor-1 α (HIF-1 α) in high glucose cells than in normal glucose cells. Inhibition of HIF-1 attenuated the expression of fibronectin induced by hypoxia in high-glucose cells. Consistently, UUO induced significantly higher HIF-1α expression along with fibrosis in diabetic mice kidneys than in nondiabetic kidneys. The increased expression of fibrosis induced by UUO in diabetic mice was diminished in proximal tubule-HIF-1α-knockout mice. Together, these results indicate that diabetes sensitizes kidney tissues and cells to fibrogenesis probably by enhancing HIF-1 activation.
(© 2022 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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