Involvement of SIRT1 in amelioration of schistosomiasis-induced hepatic fibrosis by genistein
| Autor: | Weifeng Huang, Decheng Wang, Cairong Ding, Shi Yu, Debing Du, Dan Li, Qiulin Yuan, Cao Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis medicine.medical_specialty Veterinary (miscellaneous) 030231 tropical medicine Genistein 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Antigen Downregulation and upregulation Sirtuin 1 In vivo Fibrosis Internal medicine Gene expression medicine Hepatic Stellate Cells Animals Schistosomiasis biology Schistosoma japonicum food and beverages 030108 mycology & parasitology biology.organism_classification medicine.disease Infectious Diseases Endocrinology chemistry Liver Insect Science Parasitology Hepatic fibrosis |
| Zdroj: | Acta tropica. 220 |
| ISSN: | 1873-6254 |
| Popis: | Previous study revealed that genistein alleviate the extent of hepatic fibrosis in schistosomiasis-infected mice, however, the potential mechanism is still incomplete. Present study was, therefore, carried out to investigate the underlying mechanism of ameliorating schistosomiasis-induced hepatic fibrosis by genistein. α-smooth muscle actin (α-SMA) expression, as a critical fibrotic marker, was markedly upregulated in Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis, and gradually inhibited by genistein administration in infected mice. Contrary to the changes of α-SMA expression, hepatic SIRT1 expression and activity was greatly inhibited in mice upon S. japonicum infection, and the repression was reversed in liver tissues after receiving 25 mg/kg genistein. 50 mg/kg genistein treatment gave rise to the higher SIRT1 expression and activity than that of the control group. In hepatic stellate cells (HSCs), genistein (5, 10, 20 μM) treatment resulted in the increases of SIRT1 expression and activity in concentration-dependent manner. Moreover, to mimic the fibrogenesis in vivo, macrophage was treated with soluble egg antigen (SEA) to obtain macrophage-conditioned medium (MφCM), which was used to stimulate HSCs. Intriguingly, SIRT1 overexpression decreased fibrosis associated gene expression in HSCs exposed to MφCM or not. Additionally, MφCM gave rise to high levels of α-SMA and p-Smad3 and the increments were reversed upon genistein treatment in HSCs. Furthermore, EX527, SIRT1 specific inhibitor, abrogated the inhibitory effects of genistein on HSCs activation. Together, the results support the notion that the strong elevation of SIRT1 expression and activity may represent a potential mechanism of protection against schistosomiasis-induced hepatic fibrosis by genistein. |
| Databáze: | OpenAIRE |
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