KCa3.1 Mediates Dysregulation of Mitochondrial Quality Control in Diabetic Kidney Disease

• DOI: 10.3389/fcell.2021.573814
• Publication Date: 2021-02-20T23:13:01Z
• Authors: Chunling Huang; Hao Yi; Ying Shi; Qinghua Cao; Yin Shi; Delfine Cheng; Filip Braet; Xin-Ming Chen; Carol A. Pollock
• Keywords: PINK1; Mitochondrial ROS

Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease. quality control primarily mediated by mitochondrial turnover and repair through fission/fusion mitophagy. We have previously shown that blockade calcium-activated potassium channel KCa3.1 ameliorates renal fibrosis. However, mechanistic link between disease not yet known. Transforming growth factor β1 (TGF-β1) plays a central role Recent studies indicate an emerging TGF-β1 regulation function. molecular mechanism mediating response to remains limited. In this study, function was assessed TGF-β1-exposed proximal tubular epithelial cells (HK2 cells) transfected with scrambled siRNA or siRNA. vivo , diabetes induced KCa3.1+/+ KCa3.1−/− mice low-dose streptozotocin (STZ) injection. fission/fusion-related proteins mitophagy markers, as well BCL2 interacting protein 3 (BNIP3) (a regulator) were examined HK2 kidneys. The vitro results showed significantly inhibited ATP production rate increased ROS (mtROS) when compared control, which normalized gene silencing. Increased fission suppressed fusion found both TGF-β1-treated mice, reversed deficiency. Furthermore, our models deficiency restored abnormal inhibiting BNIP3 expression TGF-β1-induced mice. Collectively, these mediates dysregulation