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Role of follistatin-like protein 1 in liver diseases.

ABSTRACT: Liver diseases, including viral hepatitis, fatty liver, metabolic-associated fatty liver disease, liver cirrhosis, alcoholic liver disease, and liver neoplasms, are major global health challenges. Despite the continued development of new drugs and technologies, the prognosis of end-stage liver diseases, including advanced liver cirrhosis and liver neoplasms, remains poor. Follistatin-like protein 1 (FSTL1), an extracellular glycoprotein, is secreted by various cell types. It is a glycoprotein that belongs to the family of secreted proteins acidic and rich in cysteine (SPARC). It is also known as transforming growth factor-beta inducible TSC-36 and follistatin-related protein (FRP). FSTL1 plays a key role in cell survival, proliferation, differentiation, and migration, as well as the regulation of inflammation and immunity. Studies have demonstrated that FSTL1 significantly affects the occurrence and development of liver diseases. This article reviews the role and mechanism of FSLT1 in liver diseases.

SUBMITTER: Gu C

PROVIDER: S-EPMC10107393 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Role of follistatin-like protein 1 in liver diseases.

Gu Chuansha C Xue Hua H Yang Xiaoli X Nie Yu Y Qian Xinlai X

Experimental biology and medicine (Maywood, N.J.) 20221219 3

Liver diseases, including viral hepatitis, fatty liver, metabolic-associated fatty liver disease, liver cirrhosis, alcoholic liver disease, and liver neoplasms, are major global health challenges. Despite the continued development of new drugs and technologies, the prognosis of end-stage liver diseases, including advanced liver cirrhosis and liver neoplasms, remains poor. Follistatin-like protein 1 (FSTL1), an extracellular glycoprotein, is secreted by various cell types. It is a glycoprotein th ...[more]

PMID: 36533576

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Project description:BACKGROUND:We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS:The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS:FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS:FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.

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Role of follistatin-like protein 1 in liver diseases.

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Role of follistatin-like protein 1 in liver diseases.

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