TGF-β Induces Up-Regulation of Chondroitin Sulfate Synthase 1 (CHSY1) in Nucleus Pulposus Cells Through MAPK Signaling

Abstract

Background/Aims: Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-β can stimulate sulfated GAG production in nucleus pulposus cells; however, the underlying mechanisms are poorly understood. Methods: CHSY1 expression was examined in rat nucleus pulposus treated with TGF-β using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-β and to measure the effect of c-Jun and Sp1 on TGF-β mediated CHSY1 promoter activity and CHSY1 expression. Results: TGF-β increased CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway. Knockdown of c-Jun and Sp1 decreased CHSY1 promoter activity, CHSY1 expression and sGAG accumulation induced by TGF-β. Furthermore, we found that TGF-β-induced expression of CHSY1 was mediated through the activation of MAPK signaling. Moreover, we showed that silencing CHSY1 decreased sGAG accumulation in nucleus pulposus cells induced by TGF-β. Conclusion: Our results suggest that TGF-β induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling.

Keywords

• Nucleus pulposus
• CHSY1
• TGF-β
• MAPK