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International Journal of Molecular Sciences

International Journal of Molecular Sciences

IF: 5.6
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The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3

Published:27 February 2024 DOI: 10.3390/ijms25052735 PMID: 38473980
Yake Wang,?Xiaolong Li,?Xiaowen Guan,?Zhe Song,?Huanfei Liu,?Zhenzhen Guan,?Jianwei Wang,?Lina Zhu,?Di Zhang,?Liang Zhao,?Peitong Xie,?Xiaoyi Wei,?Ning Shang,?Ying Liu,?Zhongzhen Jin,?Zhili Ji,?Guifu Dai

Abstract

Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells' (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-β1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$9807.90

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