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miR‐30c inhibits angiogenesis by targeting delta‐like ligand 4 in liver sinusoidal endothelial cell to attenuate liver fibrosis
Author(s) -
Gu Tianyi,
Shen Bo,
Li Binghang,
Guo Yuecheng,
Li Fei,
Ma Zhenzeng,
Chen Liuying,
Zhang Qidi,
Qu Ying,
Dong Hui,
Cai Xiaobo,
Lu Lungen
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002694r
Subject(s) - liver fibrosis , angiogenesis , cancer research , ligand (biochemistry) , fibrosis , medicine , chemistry , pathology , receptor
Liver fibrosis is a common feature of liver dysfunction during chronic liver diseases and is frequently associated with angiogenesis, a dynamic process that forms new blood vessels from preexisting vasculature. MicroRNAs (miRNAs), which act as posttranscriptional regulators of gene expression, have been shown to regulate liver fibrosis; however, how miRNAs regulate angiogenesis and its mechanism in fibrosis are not well understood. We aimed to elucidate the role and mechanism of miR‐30c in attenuating liver fibrosis. Using miRNA profiling of fibrotic murine livers, we identified differentially regulated miRNAs and discovered that miR‐30c is aberrantly expressed and targets endothelial delta‐like ligand 4 (DLL4) in either carbon tetrachloride‐treated or bile duct ligated fibrotic mice, as well as in patients with liver fibrosis. Using CCK‐8, wound healing and Matrigel tube formation assays, we found that miR‐30c inhibited liver sinusoidal endothelial cell (LSEC) proliferation, migration, and angiogenesis capacity by targeting DLL4 in vitro. Importantly, nanoparticle‐based delivery of miR‐30c to LSECs inhibited the DLL4/Notch pathway and angiogenesis, thereby ameliorating liver fibrosis in vivo. Collectively, our findings demonstrate a protective role of miR‐30c in liver fibrosis by regulating DLL4/Notch signaling and angiogenesis. Thus, miR‐30c may serve as a potential treatment for chronic liver diseases.