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Regulation of Xylosyltransferase I Gene Expression by Interleukin 1 beta in Human Primary Chondrocyte Cells MECHANISM AND IMPACT ON PROTEOGLYCAN SYNTHESIS

Abstract : Xylosyltransferase I (XT-I) is an essential enzyme of proteoglycan (PG) ă biosynthesis pathway catalyzing the initial and rate-limiting step in ă glycosaminoglycan chain assembly. It plays a critical role in the ă regulation of PG synthesis in cartilage; however, little is known about ă underlying mechanism. Here, we provide evidence that, in human primary ă chondrocytes, IL-1 beta regulates XT-I gene expression into an early ă phase of induction and a late phase of down-regulation. Based on ă promoter deletions, the region up to -850 bp was defined as a major ă element of XT-I gene displaying both constitutive and IL-1 ă beta-regulated promoter activity. Point mutation and signaling analyses ă revealed that IL-1 beta-induced promoter activity is achieved through ă AP-1 response elements and mediated by SAP/JNK and p38 signaling ă pathways. Transactivation and chromatin immunoprecipitation assays ă indicated that AP-1 is a potent transactivator of XT-I promoter and that ă IL-1 beta-induced activity is mediated through increased recruitment of ă AP-1 to the promoter. Finally, we show that Sp3 is a repressor of XT-I ă promoter and bring evidence that the repressive effect of IL-1 beta ă during the late phase is mediated through Sp3 recruitment to the ă promoter. This suggests that modulation of Sp3 in cartilage could ă prevent IL-1 beta inhibition of PG synthesis and limit tissue ă degradation.
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https://hal.univ-lorraine.fr/hal-01464669
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Submitted on : Friday, February 10, 2017 - 1:23:44 PM
Last modification on : Tuesday, October 13, 2020 - 10:46:36 AM

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Mostafa Khair, Mustapha Bourhim, Lydia Barre, Dong Li, Patrick Netter, et al.. Regulation of Xylosyltransferase I Gene Expression by Interleukin 1 beta in Human Primary Chondrocyte Cells MECHANISM AND IMPACT ON PROTEOGLYCAN SYNTHESIS. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, 288 (3), pp.1774-1784. ⟨10.1074/jbc.M112.419887⟩. ⟨hal-01464669⟩

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