The flavo-oxidase QSOX1 supports vascular smooth muscle cell migration and proliferation: Evidence for a role in neointima growth

Biochimica Et Biophysica Acta
Beatriz E BorgesLia S Nakao

Abstract

Quiescin sulfhydryl oxidase 1 (QSOX1) is a flavoenzyme largely present in the extracellular milieu whose physiological functions and substrates are not known. QSOX1 has been implicated in the regulation of tumor cell survival, proliferation and migration, in addition to extracellular matrix (ECM) remodeling. However, data regarding other pathophysiological conditions are still lacking. Arterial injury by balloon catheter is an established model of post-angioplasty restenosis. This technique induces neointima formation due to migration and proliferation of vascular smooth muscle cells (VSMC), followed by ECM synthesis and remodeling. Here, we show that QSOX1 knockdown inhibited VSMC migration and proliferation in vitro. In contrast, QSOX1 overexpression stimulated these processes. While migration could be induced by the incubation of cells with the active recombinant QSOX1, proliferation was induced by addition of the active and also of an inactive mutant QSOX1 protein. The proliferation induced by both recombinants was independent of intracellular hydrogen peroxide and dependent of the MEK/ERK pathway. To recapitulate in vivo VSMC pathophysiology, balloon-induced arterial injury was performed. The expression of QSOX1 in the neo...Continue Reading

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Citations

Jan 23, 2017·Free Radical Biology & Medicine·Leonardo Y Tanaka, Francisco R M Laurindo
Jan 8, 2020·Antioxidants & Redox Signaling·Leonardo Y TanakaFrancisco R M Laurindo
Feb 25, 2017·Journal of Hypertension·Priyanka NandakumarAravinda Chakravarti

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