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

Background/Aims: Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-beta 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-beta using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-beta and to measure the effect of c-Jun and Sp1 on TGF-beta mediated CHSY1 promoter activity and CHSY1 expression. Results: TGF-beta 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-beta. Furthermore, we found that TGF-beta-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-beta. Conclusion: Our results suggest that TGF-beta induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling. Copyright (C) 2015 S. Karger AG, Basel