7Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China4Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China2Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China3These authors contributed equally to this work.1Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China6Department of Health Care Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China5Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
Background Posttranslational modifications of albumin occur in liver diseases; however, little is known about the source and function of sulfonated albumin, a significant modification of albumin occurring in nonalcoholic fatty liver disease . We aimed to investigate the mechanism underlying sulfonated albumin production and its role in the progression of NAFLD-related liver fibrosis. Methods Serum samples from healthy controls and patients with NAFLD were used to measure the proportion of sulfo...更多
Background Posttranslational modifications of albumin occur in liver diseases; however, little is known about the source and function of sulfonated albumin, a significant modification of albumin occurring in nonalcoholic fatty liver disease . We aimed to investigate the mechanism underlying sulfonated albumin production and its role in the progression of NAFLD-related liver fibrosis. Methods Serum samples from healthy controls and patients with NAFLD were used to measure the proportion of sulfonated albumin. Mice models with NAFLD fed with high-fat diet and methionine choline-deficient diet were constructed. RNA sequencing, KEGG analysis, and GSEA were used to explore the mechanism of sulfonated albumin production and its mechanism of activating hepatic stellate cells and promoting the progression of liver fibrosis in NAFLD. Results Sulfonated albumin levels increased significantly in both human and mouse NAFLD serum samples. In vivo studies in mice have shown that the intraperitoneal injection of sulfonated albumin promotes inflammation, hepatic steatosis, and liver fibrosis in NAFLD. In addition, autophagy has been verified as a key mechanism in the regulation of sulfonated albumin production. We also demonstrated that reactive oxygen species production depends on the accumulation of damaged mitochondria and affects the production of sulfonated albumin under the regulation of autophagy. Hepatocyte-derived sulfonated albumin activates HSCs through the GAL3 receptor, thereby activating the endoplasmic reticulum stress pathway and promoting profibrotic activation of HSCs. Conclusions Our study demonstrated that sulfonated albumin activated HSCs through GAL3, thereby accelerating NAFLD-related liver fibrosis. Serum sulfonated albumin may be a potential diagnostic marker for liver fibrosis and an important target for the treatment of NAFLD-related liver fibrosis.收起
