{"title":"外泌体衍生的靶向小窝蛋白-1的miR-107通过调节肝胆胆固醇分泌途径促进胆结石进展。","authors":"Xinxing Wang, Mingze Ma, Lichao Zhu, Chuan Qin, Shuai Shao, Xianwen Xu, Ruxin Gao, Zhenhai Zhang","doi":"10.1016/j.bcp.2024.116735","DOIUrl":null,"url":null,"abstract":"<p><p>Cholesterol gallstone is a disease with high incidence and quality of life. This study aimed to investigate the function of exosome-derived miRNA in gallstone formation and its related molecular mechanism. Exosomes were extracted and isolated from patients with gallbladder stones and age- and gender-matched healthy controls, and exosomal miRNA expression was compared between the two groups. The function of exosomal miR-107 in gallstone formation was evaluated using a lithogenic fed-induced gallstone mouse model. We used a dual luciferase reporter assay to identify the miR-107 target gene. Expression of BSEP and CYP7A1 were detected using Western Blot and immunohistochemical staining to ascertain the role of miR-107 in bile acid transport and cholesterol synthesis. Bile acids, phospholipids, cholesterol and triglycerides were determined with the kit, and cholesterol saturation index was calculated. Liver cholesterol transport-related genes, phospholipid transport-related genes, liver bile salt transport-related genes, sodium-dependent bile acid transporters and organic solute transporters were detected by q-PCR. Exosomal miR-107 high expression was significant in people with gallstones. Inhibitor of miR-107 reduced lithogenic diet-induced gallstone formation in mice. MiR-107 directly inhibited caveolin-1 expression. Inhibition of caveolin-1 reduced the BSEP function. After treatment of miR-107 inhibitor, the expression of BSEP and CYP7A1 was significantly increased compared with gallbladder stones model, but the concentration of bile acid in gallbladder was significantly decreased. miR-107 altered biliary and liver lipid profiles and increased biliary cholesterol saturation index (CSI). Inhibited miR-107 promoted liver homeostasis-related cholesterol and the expression of bile acid transporters. This study revealed that exosome-derived miR-107 promoted gallstone progression by regulating the hepatobiliary cholesterol secretion pathway through targeting caveolin-1.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"232 ","pages":"116735"},"PeriodicalIF":5.3000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exosome-derived miR-107 targeting caveolin-1 promotes gallstone progression by regulating the hepatobiliary cholesterol secretion pathway.\",\"authors\":\"Xinxing Wang, Mingze Ma, Lichao Zhu, Chuan Qin, Shuai Shao, Xianwen Xu, Ruxin Gao, Zhenhai Zhang\",\"doi\":\"10.1016/j.bcp.2024.116735\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cholesterol gallstone is a disease with high incidence and quality of life. This study aimed to investigate the function of exosome-derived miRNA in gallstone formation and its related molecular mechanism. Exosomes were extracted and isolated from patients with gallbladder stones and age- and gender-matched healthy controls, and exosomal miRNA expression was compared between the two groups. The function of exosomal miR-107 in gallstone formation was evaluated using a lithogenic fed-induced gallstone mouse model. We used a dual luciferase reporter assay to identify the miR-107 target gene. Expression of BSEP and CYP7A1 were detected using Western Blot and immunohistochemical staining to ascertain the role of miR-107 in bile acid transport and cholesterol synthesis. Bile acids, phospholipids, cholesterol and triglycerides were determined with the kit, and cholesterol saturation index was calculated. Liver cholesterol transport-related genes, phospholipid transport-related genes, liver bile salt transport-related genes, sodium-dependent bile acid transporters and organic solute transporters were detected by q-PCR. Exosomal miR-107 high expression was significant in people with gallstones. Inhibitor of miR-107 reduced lithogenic diet-induced gallstone formation in mice. MiR-107 directly inhibited caveolin-1 expression. Inhibition of caveolin-1 reduced the BSEP function. After treatment of miR-107 inhibitor, the expression of BSEP and CYP7A1 was significantly increased compared with gallbladder stones model, but the concentration of bile acid in gallbladder was significantly decreased. miR-107 altered biliary and liver lipid profiles and increased biliary cholesterol saturation index (CSI). Inhibited miR-107 promoted liver homeostasis-related cholesterol and the expression of bile acid transporters. This study revealed that exosome-derived miR-107 promoted gallstone progression by regulating the hepatobiliary cholesterol secretion pathway through targeting caveolin-1.</p>\",\"PeriodicalId\":8806,\"journal\":{\"name\":\"Biochemical pharmacology\",\"volume\":\"232 \",\"pages\":\"116735\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-12-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bcp.2024.116735\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.bcp.2024.116735","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Exosome-derived miR-107 targeting caveolin-1 promotes gallstone progression by regulating the hepatobiliary cholesterol secretion pathway.
Cholesterol gallstone is a disease with high incidence and quality of life. This study aimed to investigate the function of exosome-derived miRNA in gallstone formation and its related molecular mechanism. Exosomes were extracted and isolated from patients with gallbladder stones and age- and gender-matched healthy controls, and exosomal miRNA expression was compared between the two groups. The function of exosomal miR-107 in gallstone formation was evaluated using a lithogenic fed-induced gallstone mouse model. We used a dual luciferase reporter assay to identify the miR-107 target gene. Expression of BSEP and CYP7A1 were detected using Western Blot and immunohistochemical staining to ascertain the role of miR-107 in bile acid transport and cholesterol synthesis. Bile acids, phospholipids, cholesterol and triglycerides were determined with the kit, and cholesterol saturation index was calculated. Liver cholesterol transport-related genes, phospholipid transport-related genes, liver bile salt transport-related genes, sodium-dependent bile acid transporters and organic solute transporters were detected by q-PCR. Exosomal miR-107 high expression was significant in people with gallstones. Inhibitor of miR-107 reduced lithogenic diet-induced gallstone formation in mice. MiR-107 directly inhibited caveolin-1 expression. Inhibition of caveolin-1 reduced the BSEP function. After treatment of miR-107 inhibitor, the expression of BSEP and CYP7A1 was significantly increased compared with gallbladder stones model, but the concentration of bile acid in gallbladder was significantly decreased. miR-107 altered biliary and liver lipid profiles and increased biliary cholesterol saturation index (CSI). Inhibited miR-107 promoted liver homeostasis-related cholesterol and the expression of bile acid transporters. This study revealed that exosome-derived miR-107 promoted gallstone progression by regulating the hepatobiliary cholesterol secretion pathway through targeting caveolin-1.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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