Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2

• DOI: 10.1038/s12276-024-01213-2
• Publication Date: 2024-04-16T01:03:17Z
• Authors: Eun-Ho Lee; Jae-Ho Lee; Do-Young Kim; Young-Seung Lee; Yunju Jo; Tam Dao; Kyung Eun Kim; Dae-Kyu Song; Ji Hae Seo; Young-Kyo Seo; Je Kyung Seong; Changjong Moon; Eugene Han; Mi Kyung Kim; Seungwan Ryu; Minsang Shin; Gu Seob Roh; Hye Ra Jung; Timothy F. Osborne; Dongryeol Ryu; Tae-Il Jeon; Seung-Soon Im
• Keywords: Hepatic stellate cell; Liver X receptor

Abstract Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis highly increased nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation NASH animal models patients have not been fully elucidated. In this study, we examined role of regulation LCN2 gene expression. Wild-type knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl 4 ), subjected to lipocalin-2 (LCN2) overexpression. The progression was assessed using mouse primary hepatocytes, Kupffer cells, HSCs. expression samples from normal those NASH. secretion CCl -induced liver fibrosis model, regulated transcription. Moreover, treatment holo-LCN2 stimulated intracellular iron accumulation fibrosis-related HSCs, but these effects observed 1cKO indicating that SREBP-1c-induced could stimulate HSCs through accumulation. Furthermore, strongly correlated inflammation Our findings indicate Lcn2 expression, contributing diet-induced Reduced protects against development. Therefore, establishes new connection between metabolism, affecting activation. These may lead therapeutic strategies for