Skip to main content
Top
Published in: Irish Journal of Medical Science (1971 -) 4/2020

01-11-2020 | Original Article

Research on promoting liver fibrosis injury by the targeted regulation of miR-202 for HGF to activate HSC

Authors: Xianli Niu, Shirong Nong, Junyuan Gong, Xin Zhang, Hui Tang, Tianhong Zhou, Wei Li

Published in: Irish Journal of Medical Science (1971 -) | Issue 4/2020

Login to get access

Abstract

Background

Liver fibrosis is the primary cause of liver cirrhosis and hepatocellular carcinoma and leads to considerable morbidity and mortality. Recent studies have shown that microRNAs are associated with fibrotic processes in liver disorders, but the exact role of miR-202 is still unclear, and its related mechanisms are not fully understood.

Aims

The aim of this research is to analyze the regarded regulation of miR-202 on HGF and its role in the pathological progress of liver fibrosis.

Methods

In the present study, qRT-PCR was used to detect the expression level of miR-202 in serum of patients with liver fibrosis and to compare its expression in patients with different pathological stages. HGF was predicted to be the target gene of miR-202 by TargetScan and was verified by Dual-luciferase reporter gene assay. qRT-PCR and western blot were used to detect the regulatory effect of mir-202 on the mRNA and protein of HGF; effect of miR-202 on the expression of fibrosis factors α-smooth muscle actin (α-SMA), FSP1, and collagen was detected; effect of miR-202 on liver fibrosis in mice was detected by establishing CCL4-induced mouse model.

Results

We found that the expression level of miR-202 in serum of patients with liver fibrosis was significantly higher than that of healthy people, and increased with the increase of fibrosis; miR-202 inhibited the expression level of mRNA and protein of HGF by combining with the 3’-UTR of HGF; the expression level of miR-202 significantly increased after hepatic stellate cells (HSC) were stimulated by AngII; the overexpression of miR-202 could up-regulate the expression of fibrotic factors α-SMA, FSP1, and collagen I. In addition, miR-202 up-regulated the expression of collagen I and collagen III in liver tissue of mice with liver fibrosis and promoted the progress of liver fibrosis.

Conclusions

miR-202 could negatively regulate the expression of target gene HGF, activated HSC, and increased the expression levels of various fibrosis factors, and the pathological process of liver fibrosis injury was promoted.
Literature
1.
go back to reference Yang XZ, Gen AW, Xian JC, Xiao L (2018) Diagnostic value of various noninvasive indexes in the diagnosis of chronic hepatic fibrosis. Eur Rev Med Pharmacol Sci 22(2):479–485PubMed Yang XZ, Gen AW, Xian JC, Xiao L (2018) Diagnostic value of various noninvasive indexes in the diagnosis of chronic hepatic fibrosis. Eur Rev Med Pharmacol Sci 22(2):479–485PubMed
2.
go back to reference Bilezikçi B, Haberal AN, Demirhan B (2016) Hepatocyte growth factor in patients with three different stages of chronic liver disease including hepatocellular carcinoma, cirrhosis and chronic hepatitis: an immunohistochemical study. 15(3):159 Bilezikçi B, Haberal AN, Demirhan B (2016) Hepatocyte growth factor in patients with three different stages of chronic liver disease including hepatocellular carcinoma, cirrhosis and chronic hepatitis: an immunohistochemical study. 15(3):159
3.
go back to reference Ge L, Shi B, Song YE, Li Y, Wang S, Wang X (2015) Clinical value of real-time elastography quantitative parameters in evaluating the stage of liver fibrosis and cirrhosis. Exp Ther Med 10(3):983–990PubMedPubMedCentral Ge L, Shi B, Song YE, Li Y, Wang S, Wang X (2015) Clinical value of real-time elastography quantitative parameters in evaluating the stage of liver fibrosis and cirrhosis. Exp Ther Med 10(3):983–990PubMedPubMedCentral
4.
go back to reference Xinguang Y, Huixing Y, Linlin W, Wanxin W, Xiaojun W, Linghua Y (2016) RSPOs facilitated HSC activation and promoted hepatic fibrogenesis. Oncotarget. 7(39):63767–63778 Xinguang Y, Huixing Y, Linlin W, Wanxin W, Xiaojun W, Linghua Y (2016) RSPOs facilitated HSC activation and promoted hepatic fibrogenesis. Oncotarget. 7(39):63767–63778
5.
go back to reference Wu K, Ye C, Lin L et al (2016) Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT. Clin Sci (Lond) 130(16):1469–1480 Wu K, Ye C, Lin L et al (2016) Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT. Clin Sci (Lond) 130(16):1469–1480
6.
go back to reference Tjomsland V, Aasrum M, Christoffersen T, Gladhaug IP (2017) Functional heterogeneity in tumor-derived human pancreatic stellate cells: differential expression of HGF and implications for mitogenic signaling and migration in pancreatic cancer cells. Oncotarget. 8(42):71672–71684PubMedPubMedCentral Tjomsland V, Aasrum M, Christoffersen T, Gladhaug IP (2017) Functional heterogeneity in tumor-derived human pancreatic stellate cells: differential expression of HGF and implications for mitogenic signaling and migration in pancreatic cancer cells. Oncotarget. 8(42):71672–71684PubMedPubMedCentral
7.
go back to reference Hultberg A, Morello V, Huyghe L, de Jonge N, Blanchetot C, Hanssens V, de Boeck G, Silence K, Festjens E, Heukers R, Roux B, Lamballe F, Ginestier C, Charafe-Jauffret E, Maina F, Brouckaert P, Saunders M, Thibault A, Dreier T, de Haard H, Michieli P (2015) Depleting MET-expressing tumor cells by ADCC provides a therapeutic advantage over inhibiting HGF/MET signaling. Cancer Res 75(16):3373–3383PubMed Hultberg A, Morello V, Huyghe L, de Jonge N, Blanchetot C, Hanssens V, de Boeck G, Silence K, Festjens E, Heukers R, Roux B, Lamballe F, Ginestier C, Charafe-Jauffret E, Maina F, Brouckaert P, Saunders M, Thibault A, Dreier T, de Haard H, Michieli P (2015) Depleting MET-expressing tumor cells by ADCC provides a therapeutic advantage over inhibiting HGF/MET signaling. Cancer Res 75(16):3373–3383PubMed
8.
go back to reference Fioroni I, Dell'Aquila E, Pantano F, Intagliata S, Caricato M, Vincenzi B, Coppola R, Santini D, Tonini G (2015) Role of c-mesenchymal-epithelial transition pathway in gastric cancer. Expert Opin Pharmacother 16(8):1195–1207PubMed Fioroni I, Dell'Aquila E, Pantano F, Intagliata S, Caricato M, Vincenzi B, Coppola R, Santini D, Tonini G (2015) Role of c-mesenchymal-epithelial transition pathway in gastric cancer. Expert Opin Pharmacother 16(8):1195–1207PubMed
9.
go back to reference Pothula SP, Xu Z, Goldstein D, Biankin AV, Pirola RC, Wilson JS, Apte MV (2016) Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer. Br J Cancer 114(3):269–280PubMedPubMedCentral Pothula SP, Xu Z, Goldstein D, Biankin AV, Pirola RC, Wilson JS, Apte MV (2016) Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer. Br J Cancer 114(3):269–280PubMedPubMedCentral
10.
go back to reference Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing. Cell. 132(1):9–14PubMed Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing. Cell. 132(1):9–14PubMed
11.
go back to reference Bruhn O, Drerup K, Kaehler M, Haenisch S, RöDer C, Cascorbi I (2016) Length variants of the ABCB1 3'-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance. Pharmacogenomics. 17(4):327–340PubMed Bruhn O, Drerup K, Kaehler M, Haenisch S, RöDer C, Cascorbi I (2016) Length variants of the ABCB1 3'-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance. Pharmacogenomics. 17(4):327–340PubMed
12.
go back to reference Sun M, Ding J, Li D, Yang G, Cheng Z, Zhu Q (2017) NUDT21 regulates 3'-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma. Cancer Lett 410:158PubMed Sun M, Ding J, Li D, Yang G, Cheng Z, Zhu Q (2017) NUDT21 regulates 3'-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma. Cancer Lett 410:158PubMed
13.
go back to reference Zhou L, Liu S, Han M et al (2018) miR-185 inhibits fibrogenic activation of hepatic stellate cells and prevents liver fibrosis. Mol Ther Nucleic Acids 10(C):91–102PubMed Zhou L, Liu S, Han M et al (2018) miR-185 inhibits fibrogenic activation of hepatic stellate cells and prevents liver fibrosis. Mol Ther Nucleic Acids 10(C):91–102PubMed
14.
go back to reference Lu L, Wang J, Lu H, Zhang G, Liu Y, Wang J, Zhang Y, Shang H, Ji H, Chen X, Duan Y, Li Y (2015) MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: a rat fibrosis model study. Biochem Biophys Res Commun 465(3):387–393PubMed Lu L, Wang J, Lu H, Zhang G, Liu Y, Wang J, Zhang Y, Shang H, Ji H, Chen X, Duan Y, Li Y (2015) MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: a rat fibrosis model study. Biochem Biophys Res Commun 465(3):387–393PubMed
15.
go back to reference Liss KH, Finck BN (2017) PPARs and nonalcoholic fatty liver disease. Biochimie. 136:65–74PubMed Liss KH, Finck BN (2017) PPARs and nonalcoholic fatty liver disease. Biochimie. 136:65–74PubMed
16.
go back to reference Ishak K, Baptista A, Bianchi L et al (1995) Histological grading and staging of hepatitis. J Hepatol 22(7):696PubMed Ishak K, Baptista A, Bianchi L et al (1995) Histological grading and staging of hepatitis. J Hepatol 22(7):696PubMed
17.
go back to reference Wang CH, Wey KC, Mo LR, Chang KK, Lin RC, Kuo JJ (2015) Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma. Asian Pac J Cancer Prev 16(9):3595–3604PubMed Wang CH, Wey KC, Mo LR, Chang KK, Lin RC, Kuo JJ (2015) Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma. Asian Pac J Cancer Prev 16(9):3595–3604PubMed
18.
go back to reference Ahmed A, Wong RJ, Harrison SA (2015) Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol 13(12):2062–2070PubMed Ahmed A, Wong RJ, Harrison SA (2015) Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol 13(12):2062–2070PubMed
19.
go back to reference Younossi Z, Henry L (2016) Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology. 150(8):1778–1785PubMed Younossi Z, Henry L (2016) Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology. 150(8):1778–1785PubMed
20.
go back to reference Guo L, Zhao Y, Yang S, Zhang H, Chen F (2014) An integrated analysis of miRNA, lncRNA, and mRNA expression profiles. Biomed Res Int 2014:345605PubMedPubMedCentral Guo L, Zhao Y, Yang S, Zhang H, Chen F (2014) An integrated analysis of miRNA, lncRNA, and mRNA expression profiles. Biomed Res Int 2014:345605PubMedPubMedCentral
21.
go back to reference Angrand PO, Vennin C, Bourhis XL, Adriaenssens E (2015) The role of long non-coding RNAs in genome formatting and expression. Front Genet 6:165PubMedPubMedCentral Angrand PO, Vennin C, Bourhis XL, Adriaenssens E (2015) The role of long non-coding RNAs in genome formatting and expression. Front Genet 6:165PubMedPubMedCentral
22.
go back to reference Barman B, Bhattacharyya SN (2015) mRNA targeting to endoplasmic reticulum precedes ago protein interaction and MicroRNA (miRNA)-mediated translation repression in mammalian cells. J Biol Chem 290(41):24650–24656PubMedPubMedCentral Barman B, Bhattacharyya SN (2015) mRNA targeting to endoplasmic reticulum precedes ago protein interaction and MicroRNA (miRNA)-mediated translation repression in mammalian cells. J Biol Chem 290(41):24650–24656PubMedPubMedCentral
23.
go back to reference Yu F, Jiang Z, Chen B, Dong P, Zheng J (2017) NEAT1 accelerates the progression of liver fibrosis via regulation of microRNA-122 and Kruppel-like factor 6. J Mol Med 95(11):1–12 Yu F, Jiang Z, Chen B, Dong P, Zheng J (2017) NEAT1 accelerates the progression of liver fibrosis via regulation of microRNA-122 and Kruppel-like factor 6. J Mol Med 95(11):1–12
24.
go back to reference Yu F, Lu Z, Huang K, Wang X, Xu Z, Chen B, Dong P, Zheng J (2016) MicroRNA-17-5p-activated Wnt/β-catenin pathway contributes to the progression of liver fibrosis. Oncotarget. 7(1):81–93PubMed Yu F, Lu Z, Huang K, Wang X, Xu Z, Chen B, Dong P, Zheng J (2016) MicroRNA-17-5p-activated Wnt/β-catenin pathway contributes to the progression of liver fibrosis. Oncotarget. 7(1):81–93PubMed
25.
go back to reference Crocco P, Montesanto A, Passarino G, Rose G (2016) Polymorphisms falling within putative miRNA target sites in the 3'UTR region of SIRT2 and DRD2 genes are correlated with human longevity. J Gerontol A Biol Sci Med Sci 71(5):586–592PubMed Crocco P, Montesanto A, Passarino G, Rose G (2016) Polymorphisms falling within putative miRNA target sites in the 3'UTR region of SIRT2 and DRD2 genes are correlated with human longevity. J Gerontol A Biol Sci Med Sci 71(5):586–592PubMed
26.
go back to reference Rao R, Nagarkatti P, Nagarkatti M (2015) Role of miRNA in the regulation of inflammatory genes in staphylococcal enterotoxin B-induced acute inflammatory lung injury and mortality. Toxicol Sci 144(2):284–297PubMedPubMedCentral Rao R, Nagarkatti P, Nagarkatti M (2015) Role of miRNA in the regulation of inflammatory genes in staphylococcal enterotoxin B-induced acute inflammatory lung injury and mortality. Toxicol Sci 144(2):284–297PubMedPubMedCentral
27.
go back to reference Ergun S, Oztuzcu S (2014) Computational analysis of 3'UTR region of CASP3 with respect to miRSNPs and SNPs in targetting miRNAs. Comput Biol Chem 53PB:235–241PubMed Ergun S, Oztuzcu S (2014) Computational analysis of 3'UTR region of CASP3 with respect to miRSNPs and SNPs in targetting miRNAs. Comput Biol Chem 53PB:235–241PubMed
28.
go back to reference Knox B, Wang Y, Rogers LJ, Xuan J, Yu D, Guan H, Chen J, Shi T, Ning B, Kadlubar SA (2018) A functional SNP in the 3'-UTR of TAP2 gene interacts with microRNA hsa-miR-1270 to suppress the gene expression. Environ Mol Mutagen 59(2):134–143PubMed Knox B, Wang Y, Rogers LJ, Xuan J, Yu D, Guan H, Chen J, Shi T, Ning B, Kadlubar SA (2018) A functional SNP in the 3'-UTR of TAP2 gene interacts with microRNA hsa-miR-1270 to suppress the gene expression. Environ Mol Mutagen 59(2):134–143PubMed
29.
go back to reference Papageorgiou I, Court MH (2017) Identification and validation of the microRNA response elements in the 3'-untranslated region of the UDP glucuronosyltransferase (UGT) 2B7 and 2B15 genes by a functional genomics approach. Biochem Pharmacol 146:199–213PubMedPubMedCentral Papageorgiou I, Court MH (2017) Identification and validation of the microRNA response elements in the 3'-untranslated region of the UDP glucuronosyltransferase (UGT) 2B7 and 2B15 genes by a functional genomics approach. Biochem Pharmacol 146:199–213PubMedPubMedCentral
30.
go back to reference Carrara D, Bernini M, Bacca A, Rugani I, Duranti E, Virdis A, Ghiadoni L, Taddei S, Bernini G (2014) Cholecalciferol administration blunts the systemic renin-angiotensin system in essential hypertensives with hypovitaminosis D. J Renin-Angiotensin-Aldosterone Syst 15(1):82–87PubMed Carrara D, Bernini M, Bacca A, Rugani I, Duranti E, Virdis A, Ghiadoni L, Taddei S, Bernini G (2014) Cholecalciferol administration blunts the systemic renin-angiotensin system in essential hypertensives with hypovitaminosis D. J Renin-Angiotensin-Aldosterone Syst 15(1):82–87PubMed
31.
go back to reference Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, Janssen J, Koppe C, Knolle P, Castoldi M, Tacke F, Trautwein C, Luedde T (2011) Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology. 53(1):209–218PubMed Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, Janssen J, Koppe C, Knolle P, Castoldi M, Tacke F, Trautwein C, Luedde T (2011) Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology. 53(1):209–218PubMed
32.
go back to reference Baroni GS, D'Ambrosio L, Curto P et al (2010) Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology. 23(5):1189–1199 Baroni GS, D'Ambrosio L, Curto P et al (2010) Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology. 23(5):1189–1199
33.
go back to reference Abergel A, Sapin V, Dif N, Chassard C, Darcha C, Marcand-Sauvant J, Gaillard-Martinie B, Rock E, Dechelotte P, Sauvant P (2006) Growth arrest and decrease of alpha-SMA and type I collagen expression by palmitic acid in the rat hepatic stellate cell line PAV-1. Dig Dis Sci 51(5):986–995PubMed Abergel A, Sapin V, Dif N, Chassard C, Darcha C, Marcand-Sauvant J, Gaillard-Martinie B, Rock E, Dechelotte P, Sauvant P (2006) Growth arrest and decrease of alpha-SMA and type I collagen expression by palmitic acid in the rat hepatic stellate cell line PAV-1. Dig Dis Sci 51(5):986–995PubMed
34.
go back to reference Zhang DS, Li YY, Chen XJ, Li YJ, Liu ZY, Xie WJ, Sun ZL (2015) BCL2 promotor methylation and miR-15a/16-1 upregulation is associated with sanguinarine-induced apoptotic death in rat HSC-T6 cells. J Pharmacol Sci 127(1):135–144PubMed Zhang DS, Li YY, Chen XJ, Li YJ, Liu ZY, Xie WJ, Sun ZL (2015) BCL2 promotor methylation and miR-15a/16-1 upregulation is associated with sanguinarine-induced apoptotic death in rat HSC-T6 cells. J Pharmacol Sci 127(1):135–144PubMed
35.
go back to reference Kariya A, Furusawa Y, Yunoki T, Kondo T, Tabuchi Y (2014) A microRNA-27a mimic sensitizes human oral squamous cell carcinoma HSC-4 cells to hyperthermia through downregulation of Hsp110 and Hsp90. Int J Mol Med 34(1):334–340PubMed Kariya A, Furusawa Y, Yunoki T, Kondo T, Tabuchi Y (2014) A microRNA-27a mimic sensitizes human oral squamous cell carcinoma HSC-4 cells to hyperthermia through downregulation of Hsp110 and Hsp90. Int J Mol Med 34(1):334–340PubMed
36.
go back to reference Venugopal SK, Jiang J, Kim TH et al (2010) Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation. Am J Physiol Gastrointest Liver Physiol 298(1):101–106 Venugopal SK, Jiang J, Kim TH et al (2010) Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation. Am J Physiol Gastrointest Liver Physiol 298(1):101–106
37.
go back to reference Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, Kawada N (2012) MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 61(11):1600–1609PubMed Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, Kawada N (2012) MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 61(11):1600–1609PubMed
38.
go back to reference Kagami S (2012) Involvement of glomerular renin-angiotensin system (RAS) activation in the development and progression of glomerular injury. Clin Exp Nephrol 16(2):214–220PubMed Kagami S (2012) Involvement of glomerular renin-angiotensin system (RAS) activation in the development and progression of glomerular injury. Clin Exp Nephrol 16(2):214–220PubMed
39.
go back to reference Arteel GE (2004) "HOPE" for the liver? Mechanistic insight into the role of the renin-angiotensin system in hepatic fibrosis. Hepatology. 40(1):263–265PubMed Arteel GE (2004) "HOPE" for the liver? Mechanistic insight into the role of the renin-angiotensin system in hepatic fibrosis. Hepatology. 40(1):263–265PubMed
40.
go back to reference Finot F, Masson R, Desmots F et al (2012) Combined stimulation with the tumor necrosis factor α and the epidermal growth factor promotes the proliferation of hepatocytes in rat liver cultured slices. Int J Hepatol 2012:785786PubMedPubMedCentral Finot F, Masson R, Desmots F et al (2012) Combined stimulation with the tumor necrosis factor α and the epidermal growth factor promotes the proliferation of hepatocytes in rat liver cultured slices. Int J Hepatol 2012:785786PubMedPubMedCentral
41.
go back to reference Kong LM, Liao CG, Fei F, Guo X, Xing JL, Chen ZN (2010) Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci 101(6):1463–1470PubMed Kong LM, Liao CG, Fei F, Guo X, Xing JL, Chen ZN (2010) Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci 101(6):1463–1470PubMed
42.
go back to reference Cram EJ, Liu BD, Bjeldanes LF, Firestone GL (2001) Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter. J Biol Chem 276(25):22332–22340PubMed Cram EJ, Liu BD, Bjeldanes LF, Firestone GL (2001) Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter. J Biol Chem 276(25):22332–22340PubMed
43.
go back to reference Lemberger UJ, Penz-Österreicher M, Brenner D, Trauner M, Österreicher CH (2014) P167 lack of FSP1/S100A4 attenuates liver fibrosis in mice. J Hepatol 60(1):S122–S122 Lemberger UJ, Penz-Österreicher M, Brenner D, Trauner M, Österreicher CH (2014) P167 lack of FSP1/S100A4 attenuates liver fibrosis in mice. J Hepatol 60(1):S122–S122
44.
go back to reference Yokoyama K, Kimoto K, Itoh Y, Nakatsuka K, Matsuo N, Yoshioka H, Kubota T (2012) The PI3K/Akt pathway mediates the expression of type I collagen induced by TGF-β2 in human retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol 250(1):15–23PubMed Yokoyama K, Kimoto K, Itoh Y, Nakatsuka K, Matsuo N, Yoshioka H, Kubota T (2012) The PI3K/Akt pathway mediates the expression of type I collagen induced by TGF-β2 in human retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol 250(1):15–23PubMed
45.
go back to reference Wang BB, Cheng JY, Gao HH, Zhang Y, Chen ZN, Bian H (2010) Hepatic stellate cells in inflammation-fibrosis-carcinoma axis. Anat Rec (Hoboken) 293(9):1492–1496 Wang BB, Cheng JY, Gao HH, Zhang Y, Chen ZN, Bian H (2010) Hepatic stellate cells in inflammation-fibrosis-carcinoma axis. Anat Rec (Hoboken) 293(9):1492–1496
Metadata
Title
Research on promoting liver fibrosis injury by the targeted regulation of miR-202 for HGF to activate HSC
Authors
Xianli Niu
Shirong Nong
Junyuan Gong
Xin Zhang
Hui Tang
Tianhong Zhou
Wei Li
Publication date
01-11-2020
Publisher
Springer London
Published in
Irish Journal of Medical Science (1971 -) / Issue 4/2020
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-020-02210-w

Other articles of this Issue 4/2020

Irish Journal of Medical Science (1971 -) 4/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.