tailieunhanh - Báo cáo y học: "Modulation of transforming growth factor beta signalling pathway genes by transforming growth factor beta in human osteoarthritic chondrocytes: involvement of Sp1 in both early and late response cells to transforming growth factor beta"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Modulation of transforming growth factor beta signalling pathway genes by transforming growth factor beta in human osteoarthritic chondrocytes: involvement of Sp1 in both early and late response cells to transforming growth factor beta. | Baugé et al. Arthritis Research Therapy 2011 13 R23 http content 13 1 R23 RESEARCH ARTICLE Open Access Modulation of transforming growth factor beta signalling pathway genes by transforming growth factor beta in human osteoarthritic chondrocytes involvement of Sp1 in both early and late response cells to transforming growth factor beta Catherine Baugé 1 Olivier Cauvard1 Sylvain Leclercq2 Philippe Galéra1 Karim Boumédiene1 Abstract Introduction Transforming growth factor beta TGFp plays a central role in morphogenesis growth and cell differentiation. This cytokine is particularly important in cartilage where it regulates cell proliferation and extracellular matrix synthesis. While the action of TGFp on chondrocyte metabolism has been extensively catalogued the modulation of specific genes that function as mediators ofTGFp signalling is poorly defined. In the current study elements of the Smad component of the TGFp intracellular signalling system and TGFp receptors were characterised in human chondrocytes upon TGFp1 treatment. Methods Human articular chondrocytes were incubated with TGFp1. Then mRNA and protein levels of TGFp receptors and Smads were analysed by RT-PCR and western blot analysis. The role of specific protein 1 Sp1 was investigated by gain and loss of function inhibitor siRNA expression vector . Results We showed that TGFp1 regulates mRNA levels of its own receptors and of Smad3 and Smad7. It modulates TGFp receptors post-transcriptionally by affecting their mRNA stability but does not change the Smad-3 and Smad-7 mRNA half-life span suggesting a potential transcriptional effect on these genes. Moreover the transcriptional factor Sp1 which is downregulated by TGFp1 is involved in the repression of both TGFp receptors but not in the modulation of Smad3 and Smad7. Interestingly Sp1 ectopic expression permitted also to maintain a similar expression pattern to early response to TGFp at 24 hours of treatment. It restored the induction