Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression
| Autor: | Li-Juan Hao, Xue-Jian Gao, Jing-Ming Chen, Ji-Wen Li, Jun Fang, Yun-Zhen Chen, Guang-Zong Zhao, Long-Qiang Zhang, Xiao-Yan Xu |
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| Rok vydání: | 2015 |
| Předmět: |
Regulation of gene expression
Cell growth Integrin beta1 Integrin Apoptosis Cell Cycle Proteins General Medicine Biology Cell cycle Phosphoproteins Chondrocyte Extracellular Matrix Rats Chondrocytes medicine.anatomical_structure Gene Expression Regulation Downregulation and upregulation Cell surface receptor Genetics Cancer research medicine biology.protein Animals Receptor Cell Proliferation |
| Zdroj: | International Journal of Molecular Medicine. 35:1074-1080 |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | Chondrocytes play a critical role in the repair process of osteoarthritis, which is also known as degenerative arthritis. Integrins, as the key family of cell surface receptors, are responsible for the regulation of chondrocyte proliferation, differentiation, survival and apoptosis through the recruitment and activation of downstream adaptor proteins. Moreover, G-protein-coupled receptor kinase interacting protein-1 (GIT1) exerts its effects on cell proliferation and migration through interaction with various cytokines. It has been previously suggested that GIT1 acts as a vital protein downstream of the integrin-mediated pathway. In the present study, we investigated the effects of integrin-β1 on cell proliferation and apoptosis, as well as the underlying mechanisms in chondrocytes in vitro. Following transfection with a vector expressing integrin-β1, our results revealed that the overexpression of integrin-β1 enhanced GIT1 expression, whereas the knockdown of integrin-β1 by siRNA suppressed GIT1 expression. However, no significant effect was observed on integrin-β1 expression following the enforced overexpression of GIT1, which suggests that GIT1 is localized downstream of integrin-β1. In other words, integrin-β1 regulates the expression of GIT1. Furthermore, this study demonstrated that integrin-β1 and GIT1 increased the expression levels of aggrecan and type II collagen, thus promoting chondrocyte proliferation; however, they inhibited chondrocyte apoptosis. Taken together, our data demonstrate that integrin-β1 plays a vital role in chondrocyte proliferation, differentiation and apoptosis. GIT1 exerts effects similar to those of integrin-β1 and is a downstream target of integrin-β1. |
| Databáze: | OpenAIRE |
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