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http://dx.doi.org/10.5483/BMBRep.2020.53.11.153

Lin28a attenuates TGF-β-induced renal fibrosis  

Jung, Gwon-Soo (New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation)
Hwang, Yeo Jin (Division of Electronics & Information System, Daegu Gyeongbuk Institute of Science and Technology)
Choi, Jun-Hyuk (Division of Biotechnology, Daegu Gyeongbuk Institute of Science and Technology)
Lee, Kyeong-Min (Division of Biotechnology, Daegu Gyeongbuk Institute of Science and Technology)
Publication Information
BMB Reports / v.53, no.11, 2020 , pp. 594-599 More about this Journal
Abstract
Lin28a has diverse functions including regulation of cancer, reprogramming and regeneration, but whether it promotes injury or is a protective reaction to renal injury is unknown. We studied how Lin28a acts in unilateral ureteral obstruction (UUO)-induced renal fibrosis following unilateral ureteral obstruction, in a mouse model. We further defined the role of Lin28a in transforming growth factor (TGF)-signaling pathways in renal fibrosis through in vitro study using human tubular epithelium-like HK-2 cells. In the mouse unilateral ureteral obstruction model, obstruction markedly decreased the expression of Lin28a, increased the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin. In TGF-β-stimulated HK-2 cells, the expression of Lin28a was reduced and the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin was increased. Adenovirus-mediated overexpression of Lin28a inhibited the expression of TGF-β-stimulated type I collagen, α-SMA, vimentin and fibronectin. Lin28a inhibited TGF-β-stimulated SMAD3 activity, via inhibition of SMAD3 phosphorylation, but not the MAPK pathway ERK, JNK or p38. Lin28a attenuates renal fibrosis in obstructive nephropathy, making its mechanism a possible therapeutic target for chronic kidney disease.
Keywords
Lin28a; Renal fibrosis; Renal tubular epithelial cell; SMAD3; TGF-beta signaling;
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