English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Objective— TGFβ and proliferation/phenotypic switching of smooth muscle cells (SMCs) play a pivotal role in pathogenesis of atherosclerotic and restenotic lesions after angioplasty. We have previously shown that the protein inhibitor of activated STAT (PIAS)1 activates expression of SMC differentiation marker genes including smooth muscle (SM) α-actin by interacting with serum response factor (SRF) and class I bHLH proteins. Here, we tested the hypothesis that TGFβ activates SM α-actin through PIAS1.Methods and Results— An siRNA specific for PIAS1 and ubc9, an E2-ligase for sumoylation, inhibited TGFβ-induced expression of SM α-actin in cultured SMCs as determined by real-time RT-PCR. Overexpression of PIAS1 increased SM α-actin promoter activity in a TGFβ control element (TCE)-dependent manner. Because the TCE within the SM α-actin promoter could mediate repression through interaction with KLF4, we tested whether PIAS1 regulates the function of KLF4 for SMC gene expression. PIAS1 interacted with KLF4 in mammalian two-hybrid and coimmunoprecipitation assays, and overexpression of PIAS1 inhibited KLF4-repression of SM α-actin promoter activity. Moreover, PIAS1 promoted degradation of KLF4 through sumoylation.Conclusions— These results provide evidence that PIAS1 promotes TGFβ-induced activation of SM α-actin gene expression at least in part by promoting sumoylation and degradation of the TCE repressor protein, KLF4.

PIAS1 Mediates TGFβ-Induced SM α-Actin Gene Expression Through Inhibition of KLF4 Function-Expression by Protein Sumoylation