Leptin up-regulates microRNA-27a/b-3p level in hepatic stellate cells

Journal Article · Tue May 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.03.015· OSTI ID:23082395

Li, Ziqiang; Ji, Li; Su, Shengyan; Zhu, Xiaofei; Cheng, Fangyun; Jia, Xin; Zhou, Qian; Zhou, Yajun ^[1]

---

1. Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Qi xiou road 19, Nantong, Jiangsu, 226001 (China)

Highlights: • Leptin up-regulates miR-27a/b-3p levels in hepatic stellate cells (HSCs). • Multiple signaling pathways mediate the effect of leptin on miR-27a/b-3p. • miR-27a/b-3p reduce SREBP1c and LXRα levels, and inhibit HSC activation. • miR-27a/b-3p involved in leptin-associated liver fibrosis. Obese patients, often accompanied by hyperleptinemia, are prone to liver fibrogenesis. Leptin is an adipocyte-derived hormone and plays a promotion role in liver fibrosis. Sterol regulatory element binding protein-1c (SREBP1c) exerts a crucial role in inhibiting hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Our previous studies indicated that leptin inhibited SREBP1c expression, contributing to leptin-induced HSC activation and liver fibrosis. microRNAs (miR) have emerged as important layers of regulatory control and regulate gene expression, and are implicated in numerous diseases. The present study revealed leptin up-regulation of miR-27a/b-3p levels in HSCs in vitro and in vivo. Three signaling pathways were required for leptin regulation of miR-27a/b-3p levels. miR-27a/b-3p could reduce SREBP1c and liver x receptor α (LXRα) levels, increased α-smooth muscle actin (α-SMA, a marker for HSC activation) and α1(I)collagen levels in cultured HSCs. miR-27a/b-3p regulation of SREBP1c and LXRα were independent of 3′-untranslated region of SREBP1c and LXRα mRNA. In vivo experiments further demonstrated the miR-27a/b-3p involved in leptin-associated decrease in SREBP1 level in HSCs, HSC activation, and liver fibrosis. These data might have potential implications for our understanding of molecular mechanisms underlying leptin roles in liver fibrogenesis of obese patients with hyperleptinaemia.

• OSTI ID: 23082395
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 366; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
COLLAGEN
IN VITRO
IN VIVO
LEPTIN
LIVER
MESSENGER-RNA