TGF-β Mediates Renal Fibrosis via the Smad3-Erbb4-IR Long Noncoding RNA Axis
Publication in refereed journal

替代計量分析
.

其它資訊
摘要Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling. Mechanistic studies revealed that Smad7, a downstream negative regulator of TGF-β/Smad signaling, is a target gene of Erbb4-IR because a binding site of Erbb4-IR was found on the 3' UTR of Smad7 gene. Mutation of this binding site prevented the suppressive effect of Erbb4-IR on the Smad7 reporter activity; in contrast, overexpression of Erbb4-IR largely inhibited Smad7 but increased collagen I and α-SMA transcriptions. Thus, kidney-specific silencing of Erbb4-IR upregulated renal Smad7 and thus blocked TGF-β/Smad3-mediated renal fibrosis in vivo and in vitro. In conclusion, the present study identified that Erbb4-IR is a novel lncRNA responsible for TGF-β/Smad3-mediated renal fibrosis by downregulating Smad7. Targeting Erbb4-IR may represent a precise therapeutic strategy for progressive renal fibrosis.
出版社接受日期29.09.2017
著者Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
期刊名稱Molecular Therapy
出版年份2018
月份1
日期3
卷號26
期次1
頁次148 - 161
國際標準期刊號1525-0016
電子國際標準期刊號1525-0024
語言英式英語

上次更新時間 2021-13-10 於 23:37