Geng Qin1, Guo Zhen Wang2, Dan Dan Guo3, Ru Xue Bai1, Miao Wang1, Shi Yu Du1. 1. Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China. 2. Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China. 3. Department of Ultrasonography, China-Japan Friendship Hospital, Beijing, China.
Abstract
OBJECTIVE: To explore the effects of mothers against decapentaplegic homolog family member 4 (Smad4) deletion on inflammation and fibrogenesis in nonalcoholic steatohepatitis (NASH). METHODS: Biopsied liver samples from NASH patients and normal liver tissue samples from patients who had received liver resection for trauma were collected. Smad4Co/Co and wild-type (WT) mice were used to construct the NASH model using a high-fat diet (HFD) or methionine- and choline-deficient diet (MCD). HE staining and TUNEL assay were used to observe the pathological changes and cell apoptosis, respectively. Quantitative real-time polymerase chain reaction was used to detect the expression of inflammatory, fibrogenesis and apoptosis-related genes, and immunohistochemistry to determine the protein expression of SMAD4, MCP-1 and α-SMA. RESULTS: SMAD4 protein expression significantly increased in NASH patients than in the control group. Compared with WT mice, HFD- and MCD-fed Smad4Co/Co mice showed decreased hepatic steatosis, inflammation, liver cell apoptosis and nonalcoholic fatty liver activity score, reduced plasma glucose, triglyceride, free fatty acids, alanine aminotransferase and aspartate aminotransferase levels but increased adiponectin. Moreover, Smad4Co/Co decreased the expression of inflammatory markers (TNF-α, MCP-1, IFN-γ), fibrogenetic markers (COL1A1, α-SMA and TGF-β1), lipogenic (Srebp1c, Fas and Acc) and proapoptotic genes (Bax and caspase-3), but increased the expression of β-oxidation (Ppar-α, Cpt1 and Aco) and antiapoptotic genes (Bcl-2). CONCLUSION: Smad4 deletion may inhibit lipogenesis, stimulate β-oxidation, improve lipid metabolism and liver function, alleviate inflammation and fibrosis, and reduce cell apoptosis in NASH.
OBJECTIVE: To explore the effects of mothers against decapentaplegic homolog family member 4 (Smad4) deletion on inflammation and fibrogenesis in nonalcoholic steatohepatitis (NASH). METHODS: Biopsied liver samples from NASH patients and normal liver tissue samples from patients who had received liver resection for trauma were collected. Smad4Co/Co and wild-type (WT) mice were used to construct the NASH model using a high-fat diet (HFD) or methionine- and choline-deficient diet (MCD). HE staining and TUNEL assay were used to observe the pathological changes and cell apoptosis, respectively. Quantitative real-time polymerase chain reaction was used to detect the expression of inflammatory, fibrogenesis and apoptosis-related genes, and immunohistochemistry to determine the protein expression of SMAD4, MCP-1 and α-SMA. RESULTS:SMAD4 protein expression significantly increased in NASH patients than in the control group. Compared with WT mice, HFD- and MCD-fed Smad4Co/Co mice showed decreased hepatic steatosis, inflammation, liver cell apoptosis and nonalcoholic fatty liver activity score, reduced plasma glucose, triglyceride, free fatty acids, alanine aminotransferase and aspartate aminotransferase levels but increased adiponectin. Moreover, Smad4Co/Co decreased the expression of inflammatory markers (TNF-α, MCP-1, IFN-γ), fibrogenetic markers (COL1A1, α-SMA and TGF-β1), lipogenic (Srebp1c, Fas and Acc) and proapoptotic genes (Bax and caspase-3), but increased the expression of β-oxidation (Ppar-α, Cpt1 and Aco) and antiapoptotic genes (Bcl-2). CONCLUSION:Smad4 deletion may inhibit lipogenesis, stimulate β-oxidation, improve lipid metabolism and liver function, alleviate inflammation and fibrosis, and reduce cell apoptosis in NASH.
Authors: Marwa Matboli; Shaimaa H Gadallah; Wafaa M Rashed; Amany Helmy Hasanin; Nada Essawy; Hala M Ghanem; Sanaa Eissa Journal: Int J Mol Sci Date: 2021-06-24 Impact factor: 5.923