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rSjP40抑制肝星状细胞中I型胶原启动子Ets-1的活性。

rSjP40 Inhibited the Activity of Collagen Type I Promoter Ets-1 in HSCs.

作者信息

Li Jing, Zhang Jiali, Zhang Bei, Chen Liuting, Chen Guo, Zhu Dandan, Chen Jinling, Duan Lian, Duan Yinong

机构信息

Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, China.

Cancer Research Center Nantong, Nantong Tumor Hospital & Tumor Hospital Affiliated to Nantong University, Nantong, China.

出版信息

Front Cell Dev Biol. 2021 Nov 8;9:765616. doi: 10.3389/fcell.2021.765616. eCollection 2021.

Abstract

Liver fibrosis is a severe disease characterized by excessive deposition of extracellular matrix (ECM) components in the liver. Activated hepatic stellate cells (HSCs) are a major source of ECM and a key regulator of liver fibrosis. Collagen type I alpha I (COL1A1) is one of the main components of ECM and is a major component in fibrotic tissues. Previously, we demonstrated that soluble egg antigen from could inhibit the expression of COL1A1 in activated HSCs. In addition, studies have found that Ets proto-oncogene 1 (Ets-1) suppresses the production of ECM by down-regulating matrix related genes such as induced by transforming growth factor β, and ultimately inhibits liver fibrosis. In this study, the major aim was to investigate the effect and mechanism of Ets-1 on inhibiting gene promoter activity in HSCs by recombinant protein P40 (rSjP40). We observed the rSjP40 inhibited the expression of by inhibiting the activity of the promoter, and the core region of rSjP40 acting on promoter was located at -1,722/-1,592. In addition, we also demonstrated that rSjP40 could promote the expression of Ets-1, and Ets-1 has a negative regulation effect on the promoter in human LX-2 cells. These data suggest that rSjP40 might inhibit the activity of promoter and inhibit the activation of HSCs by increasing the expression of transcription factor Ets-1, which will provide a new experimental basis for the prevention and treatment of liver fibrosis.

摘要

肝纤维化是一种严重疾病,其特征是肝脏中细胞外基质(ECM)成分过度沉积。活化的肝星状细胞(HSC)是ECM的主要来源,也是肝纤维化的关键调节因子。I型胶原蛋白α1(COL1A1)是ECM的主要成分之一,也是纤维化组织中的主要成分。此前,我们证明来自[具体来源未明确]的可溶性虫卵抗原可抑制活化HSC中COL1A1的表达。此外,研究发现Ets原癌基因1(Ets-1)通过下调转化生长因子β诱导的基质相关基因等,抑制ECM的产生,最终抑制肝纤维化。在本研究中,主要目的是通过重组[具体名称未明确]蛋白P40(rSjP40)研究Ets-1对抑制HSC中[具体基因未明确]基因启动子活性的作用及机制。我们观察到rSjP40通过抑制[具体基因未明确]启动子的活性来抑制其表达,且rSjP40作用于[具体基因未明确]启动子的核心区域位于-1,722/-1,592。此外,我们还证明rSjP40可促进Ets-1的表达,且Ets-1对人LX-2细胞中的[具体基因未明确]启动子具有负调控作用。这些数据表明,rSjP40可能通过增加转录因子Ets-1的表达来抑制[具体基因未明确]启动子的活性并抑制HSC的活化,这将为肝纤维化的防治提供新的实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/8606555/03f07f6cb34d/fcell-09-765616-g001.jpg

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