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Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is a specific regulator of fibroblast motility and contractility

Satish, L and Johnson, S and Wang, JHC and Post, JC and Ehrlich, GD and Kathju, S (2010) Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is a specific regulator of fibroblast motility and contractility. PLoS ONE, 5 (4).

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Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing Tcomplex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta) is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF) stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA) reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (α-SMA) expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less α-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular beta-actin but markedly decreased α-SMA; in contrast, reduction of CCT-beta had minimal effect on either actin isoform. Direct inhibition of α-SMA with siRNA reduced both basal and growth factor-induced fibroblast motility. These results indicate that CCT-eta is a specific regulator of fibroblast motility and contractility and may be a key determinant of the scarless wound healing phenotype by means of its specific regulation of α-SMA expression. © 2010 Satish et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Satish, Llas238@pitt.eduLAS238
Johnson, S
Wang, JHCwanghc@pitt.eduWANGHC
Post, JC
Ehrlich, GD
Kathju, S
ContributionContributors NameEmailPitt UsernameORCID
Date: 14 September 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0010063
Refereed: Yes
MeSH Headings: Age Factors; Animals; Cell Movement; Cell Size; Chaperonin Containing TCP-1--analysis; Chaperonin Containing TCP-1--biosynthesis; Chaperonin Containing TCP-1--physiology; Cicatrix; Fetus; Fibroblasts--chemistry; Fibroblasts--cytology; Gene Expression Regulation; Intercellular Signaling Peptides and Proteins--pharmacology; Protein Subunits; RNA, Small Interfering--pharmacology; Rabbits; Wound Healing
Other ID: NLM PMC2862014
PubMed Central ID: PMC2862014
PubMed ID: 20442790
Date Deposited: 03 Aug 2012 20:54
Last Modified: 02 Feb 2019 13:55


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