Cell proliferation · 2018
TGF-β1 promotes gap junctions formation in chondrocytes via Smad3/Smad4 signalling.
СтатьяНазвание и аннотация: Перевод в очереди
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Wang Qingxuan, Zhou Chenchen, Li Xiaobing, Cai Linyi, Zou Jing, Zhang Demao, Xie Jing, Lai Wenli
Аннотация
OBJECTIVES: Connexin-mediated functional gap junction intercellular communication (GJIC) has a vital role in development, homeostasis and pathology. Transforming growth factor-β1 (TGF-β1), as one of the most vital factors in chondrocytes, promotes cartilage precursor cell differentiation and chondrocyte proliferation, migration and metabolism. However, how TGF-β1 mediates GJIC in chondrocytes remains unclear. This study aims to determine the influence of TGF-β1 on GJIC in mouse chondrocytes and its underlying mechanism.
METHODS: qPCR and mRNA microarray were used to verify the expression of genes in the TGF-β and connexin families in cartilage and chondrocytes. A scrape loading/dye transfer assay was performed to explore GJIC. Western blot analysis was used to detect connexin43 (Cx43) and Smad signalling components. Immunofluorescence staining was performed to characterize protein distribution.
RESULTS: The TGF-β1 mRNA was the highest expressed member of the TGFβ super family in cartilage. TGF-β1 promoted functional GJIC through increased expression of Cx43. TGF-β1-mediated GJIC required the participation of TGF-β type I receptor. TGF-β1 activated Smad3 and Smad4 signalling to facilitate their nuclear translocation. The Smad3 and Smad4 signalling proteins bound to the promoter of Gja1 and thus initiated Cx43 gene expression.
CONCLUSIONS: For the first time, these results revealed a vital role of TGF-β1 in cell-cell communication in chondrocytes via gap junction formation. We describe the regulatory mechanism, the involvement of TGF-β type I receptor and the nuclear translocation of Smad3/4.
METHODS: qPCR and mRNA microarray were used to verify the expression of genes in the TGF-β and connexin families in cartilage and chondrocytes. A scrape loading/dye transfer assay was performed to explore GJIC. Western blot analysis was used to detect connexin43 (Cx43) and Smad signalling components. Immunofluorescence staining was performed to characterize protein distribution.
RESULTS: The TGF-β1 mRNA was the highest expressed member of the TGFβ super family in cartilage. TGF-β1 promoted functional GJIC through increased expression of Cx43. TGF-β1-mediated GJIC required the participation of TGF-β type I receptor. TGF-β1 activated Smad3 and Smad4 signalling to facilitate their nuclear translocation. The Smad3 and Smad4 signalling proteins bound to the promoter of Gja1 and thus initiated Cx43 gene expression.
CONCLUSIONS: For the first time, these results revealed a vital role of TGF-β1 in cell-cell communication in chondrocytes via gap junction formation. We describe the regulatory mechanism, the involvement of TGF-β type I receptor and the nuclear translocation of Smad3/4.