title: ZIPK is critical for the motility and contractility of VSMCs through the regulation of nonmuscle myosin II isoforms.
abstract: Migration of medial vascular smooth muscle cells (VSMCs) into the intimal layer contributes to pathological remodeling of the blood vessel in arterial hypertension and atherosclerosis. It is well established that reorganization of cytoskeletal networks is an essential component of cellular motile events. However, there is currently a lack of insight into the cellular characteristics of VSMC migration under three-dimensional environments. Here, we investigated the mechanisms of VSMC migration and remodeling using two different collagen matrix assays as in vitro models: migration of VSMCs within a collagen matrix for VSMC invasion and contraction of a collagen gel by VSMCs for VSMC remodeling and contraction. We found that nonmuscle myosin IIA (NMIIA) and nonmuscle myosin IIB (NMIIB) differentially contribute to the migratory capacity of VSMCs via NMII isoform-dependent cytoskeletal reorganization. Depletion of NMIIA by short hairpin RNA revealed a unique interplay between actomyosin and microtubules during VSMC migration. On the other hand, NMIIB was required for the structural maintenance of migrating VSMC. Interestingly, there was a significant difference between NMIIA and NMIIB knockdown in the VSMC migration but not in the VSMC-mediated collagen gel contraction. Furthermore, depletion of zipper-interacting protein kinase by short hairpin RNA resulted in an impairment of VSMC migration and a substantial decrease of VSMC-mediated collagen gel contraction. These results suggest that NMIIA and NMIIB uniquely control VSMC migration and may contribute to vascular remodeling, which are both regulated by zipper-interacting protein kinase.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komatsu
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ikebe
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D064550:Death-Associated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; C579101:DAPK3 protein, human; D064550:Death-Associated Protein Kinases; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB
keywords: cytoskeleton; migration; nonmuscle myosin II; three-dimensional; vascular smooth muscle cell; zipper-interacting protein kinase