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Oxidized low‐density lipoprotein activates extracellular signal‐regulated kinase signaling to downregulate sortilin expression in liver sinusoidal endothelial cells
Author(s) -
Zhang Qi,
Lin Wenyan,
Tian Limin,
Di Baoshan,
Yu Jing,
Niu Xiang'e,
Liu Jing
Publication year - 2021
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.15486
Subject(s) - downregulation and upregulation , oil red o , h&e stain , staining , cd31 , western blot , liver injury , biology , microbiology and biotechnology , medicine , endocrinology , pathology , immunohistochemistry , biochemistry , adipose tissue , gene , adipogenesis
Background and Aim Both type 2 diabetes mellitus and non‐alcoholic fatty liver disease are closely associated with elevated levels of low‐density lipoprotein cholesterol and its oxidized form (ox‐LDL). This study aimed to investigate the regulation of sortilin in liver tissue and its potential implications for lipid metabolism. Methods Sixty male Wistar rats were randomly divided into four groups: control group ( n = 15), ox‐LDL group ( n = 15), PD98059 group ( n = 15), and ox‐LDL + PD98059 group ( n = 15). Liver sinusoidal endothelial cells were extracted from liver tissue of the control group and were identified using an anti‐CD31 antibody. Lipid droplet accumulation was observed by Oil red O and hematoxylin–eosin staining. The protein expression levels were detected by immunohistochemical staining, real‐time reverse transcription‐polymerase chain reaction, and western blot. Histopathologic examinations were performed by Gomori methenamine silver staining. Results The ox‐LDL group exhibited increased lipid droplet accumulation. Further, ox‐LDL activated the extracellular signal‐regulated kinase (ERK)‐mediated downregulation of sortilin expression, whereas blocking of ERK signaling by PD98059 increased sortilin protein expression. Consistently, hematoxylin–eosin staining showed that the structure of the hepatocytes was loose and disordered in arrangement, with lipid droplets present in the cytoplasm of the ox‐LDL group. However, PD98059 significantly improved the integration of the scaffold structure. Gomori methenamine silver staining showed that the ox‐LDL group had darker and more obvious fragmented silver nitrate deposits in the basement membrane and sinus space. Conclusions Sortilin can protect liver sinusoidal endothelial cells from injury and maintain integration of the liver scaffold structure in ox‐LDL‐induced lipid‐injured liver.