title: Calponin 3 regulates stress fiber formation in dermal fibroblasts during wound healing.
abstract: Skin wound healing is an intricate process involving various cell types and molecules. In granulation tissue, fibroblasts proliferate and differentiate into myofibroblasts and generate mechanical tension for wound closure and contraction. Actin stress fibers formed in these cells, especially those containing α-smooth muscle actin (α-SMA), are the central machinery for contractile force generation. In the present study, calponin 3 (CNN3), which has a phosphorylation-dependent actin-binding property, was identified in the molecular mechanism underlying stress fiber formation. CNN3 was expressed by fibroblasts/myofibroblasts in the proliferation phase of wound healing, and was associated with α-SMA in stress fibers formed by cultured dermal fibroblasts. CNN3 expression was post-transcriptionally regulated by tension, as demonstrated by disruption of actin filament organization under floating culture or blebbistatin treatment. CNN3 knockdown in primary fibroblasts impaired stress fiber formation, resulting in a phenotype of decreased cellular dynamics such as cell motility and contractile ability. These findings indicate that CNN3 participates in actin stress fiber remodeling, which is required for cell motility and contraction of dermal fibroblasts in the wound healing process.
authors.affiliation: Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Daimon
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Shibukawa
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Wada
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000473:pathology; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D020405:Dermis / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006097:Granulation Tissue / Q000473:pathology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000235:genetics; D022502:Stress Fibers / Q000378:metabolism* / Q000648:ultrastructure; D014945:Wound Healing / Q000502:physiology*; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D000096985:Calponins; C541116:ACTA2 protein, human; C472645:blebbistatin