小柯机器人

美国加州大学Jerrold M. Olefsky研究组发现，MiR-690 处理可减少非酒精性脂肪性肝炎 (NASH)中的纤维化和脂肪变性，并恢复特定的枯否细胞 (KCs)功能。2022年6月13日出版的《细胞—代谢》杂志发表了这项成果。

KCs产生内源性 miR-690，并通过外泌体分泌将该 miRNA 运送到其他肝细胞，例如肝细胞、募集的肝巨噬细胞 (RHM) 和肝星状细胞 (HSC)。miR-690 直接抑制 HSC 中的纤维化、RHM 中的炎症和肝细胞中的从头脂肪生成。当在体内向 NASH 小鼠施用 miR-690 模拟物时，NASH 表型的所有特征都受到强烈抑制。在 NASH 进展过程中，KCs 缺乏 miR-690，并且小鼠和人类 NASH 肝脏中的 miR-690 水平明显低于对照组。miR-690 的 KC 特异性 KO 促进 NASH 发病。miR-690 的主要靶标是 NADK mRNA，NADK 水平与细胞 miR-690 含量成反比。

这些研究表明，KCs 在 NASH 的病因学中起着核心作用，并提高了 miR-690 可能成为这种疾病的治疗剂的可能性。

附：英文原文

Title: MiR-690 treatment causes decreased fibrosis and steatosis and restores specific Kupffer cell functions in NASH

Author: Hong Gao, Zhongmou Jin, Gautam Bandyopadhyay, Karina Cunha e Rocha, Xiao Liu, Huayi Zhao, Dinghong Zhang, Hani Jouihan, Soheil Pourshahian, Tatiana Kisseleva, David A. Brenner, Wei Ying, Jerrold M. Olefsky

Issue&Volume: 2022-06-13

Abstract: Nonalcoholic steatohepatitis (NASH) is a liver disease associated with significantmorbidity. Kupffer cells (KCs) produce endogenous miR-690 and, via exosome secretion,shuttle this miRNA to other liver cells, such as hepatocytes, recruited hepatic macrophages(RHMs), and hepatic stellate cells (HSCs). miR-690 directly inhibits fibrogenesisin HSCs, inflammation in RHMs, and de novo lipogenesis in hepatocytes. When an miR-690 mimic is administered to NASH mice in vivo, all the features of the NASH phenotype are robustly inhibited. During the developmentof NASH, KCs become miR-690 deficient, and miR-690 levels are markedly lower in mouseand human NASH livers than in controls. KC-specific KO of miR-690 promotes NASH pathogenesis.A primary target of miR-690 is NADK mRNA, and NADK levels are inversely proportionalto the cellular miR-690 content. These studies show that KCs play a central role inthe etiology of NASH and raise the possibility that miR-690 could emerge as a therapeuticfor this condition.

DOI: 10.1016/j.cmet.2022.05.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00190-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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