title: Antischistosomiasis Liver Fibrosis Effects of Chlorogenic Acid through IL-13/miR-21/Smad7 Signaling Interactions In Vivo and In Vitro.
abstract: This study investigated the antischistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on interleukin 13 (IL-13)/microRNA-21 (miR-21)/Smad7 signaling interactions in the hepatic stellate LX2 cell line and schistosome-infected mice. The transfection was based on the ability of the GV273-miR-21-enhanced green fluorescent protein (EGFP) and GV369-miR-21-EGFP lentiviral system to up- or downregulate the miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7, and connective tissue growth factor (CTGF) and the protein expression of Smad7, CTGF, Smad1, phosphor-Smad1 (p-Smad1), Smad2, p-Smad2, Smad2/3, p-Smad2/3, transforming growth factor β (TGF-β) receptor I, and α-smooth muscle actin (α-SMA) was assayed. Pathological manifestation of hepatic tissue was assessed for the degree of liver fibrosis in animals. The results showed that CGA could inhibit the mRNA expression of miR-21, promote Smad7, and inhibit CTGF mRNA expression. Meanwhile, CGA could significantly lower the protein levels of CTGF, p-Smad1, p-Smad2, p-Smad2/3, TGF-β receptor I, and α-SMA and elevate the Smad7 protein level. In vivo, with treatment with CGA, the signaling molecules of IL-13/miR-21/Smad7 interactions were markedly regulated. CGA could also reduce the degree of liver fibrosis in pathological manifestations. In conclusion, CGA could inhibit schistosomiasis-induced hepatic fibrosis through IL-13/miR-21/Smad7 signaling interactions in LX2 cells and schistosome-infected mice and might serve as an antifibrosis agent for treating schistosomiasis liver fibrosis.
authors.affiliation: School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatology, Hubei Provincial Hospital of Chinese Medicine, Wuhan, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.affiliation: School of Life Science, Hubei University, Wuhan, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Chen
authors.affiliation: School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China leizhao@hust.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D002726:Chlorogenic Acid / Q000494:pharmacology*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D055785:Gene Knockdown Techniques; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism; D012554:Schistosomiasis japonica / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051906:Smad7 Protein / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; C578095:IL13 protein, human; D018793:Interleukin-13; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D055513:Connective Tissue Growth Factor; D002726:Chlorogenic Acid
keywords: IL-13; Smad7; chlorogenic acid; liver fibrosis; miR-21; schistosomiasis