ABSTRACT
Follistatinlike 1 (Fstl1) is a secreted glycoprotein that belongs to the follistatin and SPARC (secreted protein, acidic and rich in cysteine) families and was identified to serve a critical role in lung fibrosis. However, the role of Fstl1 in liver fibrosis remains undefined. Therefore, the aim of the present study was to investigate the role of Fstl1 in liver fibrosis. The results indicated that Fstl1 was highly expressed in human hepatic fibrosis tissues and activated hepatic stellate cells (HSCs). Furthermore, knockdown of Fstl1effectively suppressed HSC proliferation and the protein expression levels of αSMA and collagen I in transforming growth factor (TGF)ß1treated HSCs. Mechanistically, knockdown of Fstl1 remarkably decreased the phosphorylation level of Smad3 in TGFß1induced HSCs. Taken together, the present study demonstrated that Fstl1serves an important role in liver fibrosis and target deletion of Fstl1 attenuated HSCs activation through suppressing TGFß1/Smad3 signaling pathway. Therefore, Fstl1 may be a potential therapeutic target for the treatment of liver fibrosis.
Subject(s)
Follistatin-Related Proteins/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Actins/metabolism , Cell Proliferation , Cells, Cultured , Collagen Type I/metabolism , Follistatin-Related Proteins/antagonists & inhibitors , Follistatin-Related Proteins/genetics , Hepatic Stellate Cells/cytology , Hepatic Stellate Cells/metabolism , Humans , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , RNA Interference , RNA, Small Interfering/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta1/pharmacology , Up-Regulation/drug effectsABSTRACT
OBJECTIVE: To analyse the relationships among HBV genotypes, HBV DNA levels and histopathological features of the livers of familial grouped hepatitis B patients in the Tianjin area. METHODS: One hundred familial grouped hepatitis B (CHB) patients were enrolled in this study. Thirty-five of the 100 patients were chronic asymptomatic HBsAg carriers (ASC) and 65/100 were mild CHB patients. Their HBV genotypes and HBV-DNA levels were detected and liver biopsies were performed for analyzing the pathological features. RESULTS: Seven patients were of HBV genotype B (7%), and most of them had a HBV DNA level in the middle 10(3-5) copies/ml (57.14%). The histopathological features of the livers were of different degrees of injury. Eleven patients HBV was of genotype BC (11%); their HBV DNA levels were from 10(3-5) copies/ml (45.45%) to 10(6-7)copies/ml (36.36%). Their liver pathology showed slight or severe injuries (< or = G2 90.91%, < or = S(2) 81.82%). Eighty-two patients HBV was of genotype C (82%), and among the 82, 29 were ASC and 53 were CHB. Among the ASC, most of them had a high HBV DNA level (72.41%), and all of them had different degrees of liver injury. Among the CHB, their HBV DNA levels were 10(6-7) copies/ml (39.62%) and more than or equal 10(8) copies/ml (49.06%). The liver histopathological features were > or = G(2) in 38 patients (71.70%), and > or = S(2) in 25 patients (47.17%). CONCLUSIONS: (1) In the majority, HBV of the family gathered hepatitis B patients living in Tianjin is of genotype C and they have a high HBV-DNA level and severe liver pathological injuries. These features of the family gathered hepatitis B patients are the main factors causing the unfavorable prognosis of the patients. (2) There is inflammation of different degrees in the livers and high HBV DNA levels in all the family gathered ASC patients. Antiviral therapy should be planned according to the pathological features in patients livers. (3) Liver biopsies should be performed routinely before their antiviral therapy.
