A Role for Polo-Like Kinase 4 in Vascular Fibroblast Cell-Type Transition

Jing Li; Go Urabe; Yitao Huang; Mengxue Zhang; Bowen Wang; Lynn Marcho; Hongtao Shen; K Craig Kent; Lian-Wang Guo

doi:10.1016/j.jacbts.2020.12.015

A Role for Polo-Like Kinase 4 in Vascular Fibroblast Cell-Type Transition

JACC Basic Transl Sci. 2021 Mar 22;6(3):257-283. doi: 10.1016/j.jacbts.2020.12.015. eCollection 2021 Mar.

Authors

Jing Li¹, Go Urabe¹, Yitao Huang¹, Mengxue Zhang^{1

2}, Bowen Wang¹, Lynn Marcho³, Hongtao Shen¹, K Craig Kent¹, Lian-Wang Guo¹

Affiliations

¹ Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
² Cellular and Molecular Pathology Graduate Program, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
³ Davis Heart and Lung Research Institute, Wexner Medical Center, Ohio State University, Columbus, Ohio, USA.

Abstract

Polo-like kinase 4 (PLK4) is canonically known for its cytoplasmic function in centriole duplication. Here we show a noncanonical PLK4 function of regulating the transcription factor SRF's nuclear activity and associated myofibroblast-like cell-type transition. In this context, we have further found that PLK4's phosphorylation and transcription are respectively regulated by PDGF receptor and epigenetic factor BRD4. Furthermore, in vivo experiments suggest PLK4 inhibition as a potential approach to mitigating vascular fibrosis.

Keywords: AA, PDGF-AA; BET, bromo/extraterminal domain–containing protein; BRD4; BRD4, bromodomain protein 4; CenB, centrinone-B; EEL, external elastic lamina; JQ1, a BET family–selective epigenetic modulator drug; MRTF-A, myocardin-related transcription factor A; PDGF receptor; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; PLK, polo-like kinase; PLK4; SRF; SRF, serum response factor; fibroblast cell-type transition; αSMA, α-smooth muscle actin.

Abstract

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