Anti-Schistosomiasis Liver Fibrosis Effect of Corilagin Through Interacting the IL-13/miR-21/smads Signaling Pathway <i> in Vitro</i> and <i> in Vivo</i>

Abstract

Background: This study was to investigate the anti-fibrosis effect of corilagin on schistosomiasis liver fibrosis through interacting IL-13/miR-21/smads signaling pathway. Methods: The cellular models were established with LX2 cells and primary mouse hepatic stellate cells stimulated by IL-13. MiR-21 was regulated up or down by lentiviral vector transfection, and smad1 and smad2 were transfected by siRNA for down-regulation. Mice were infected by schistosome cercariae as animal model. The real-time PCR was employed to detect mRNA levels of miR-21, smad7 and CTGF, and western blot was used to examine protein levels of smad7, CTGF, smad1, p-smad1, smad2, p-smad2, p-smad2/3, smad4, TβR Ⅰ and α-SMA. IL-13 and SCAg in serum were measured by ELISA. Immunohistochemistry was used to test the expression of smad7. The liver tissue was tested for hematoxylin-eosin and masson staining. Findings: No matter in normal, miR-21 up- or down-regulated LX2 cells, corilagin could inhibit the mRNA level of miR-21 and CTGF and promote smad7 mRNA level (P < 0.01 or 0.05). Meanwhile, corilagin could significantly reduce the protein level of CTGF, p-smad1, p-smad2, psmad2/3, smad4, TβRⅠand α-SMA and promote smad7 protein level (P <0.05 or 0.01). Corilagin could decrease serum IL-13 and SCAg level (P < 0.01 or 0.05), and also reduce the degree of liver fibrosis in pathological manifestations. Interpretation: Corilagin could inhibit schistosomiasis-induced hepatic fibrosis through the potential drug intervention targets in IL-13/miR21/smads pathway, which might serve as an anti-fibrosis agent for treating schistosomiasis liver fibrosis. Funding Statement: This study was supported by the National Natural Science Foundation of China (81371840), Hubei Province Health and Family Planning Scientific Research Project (WJ2017Q021), Hubei Provincial Natural Science Foundation of China (2017CFB471), the Fundamental Research Funds for the Central Universities (2017KFYXJJ238). Declaration of Interests: The authors have no financial conflicts to declare. Ethics Approval Statement: The study was reviewed and approved by the Research Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (IORG No: IORG0003571).