TGFβ1 modulated myofibroblast transformation via matrix interaction: Role in wound contraction

J. V. Jester, Walter M Petroll, J. Huang, P. Roy, P. A. Barry-Lane, Harrison D Cavanagh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose. Contraction of corneal wounds was first recognized over a decade ago as a response to wound healing following corneal surgery. Since then, studies have shown that the keratocyte undergoes a series of phenotypic alterations leading to the development or a contractile-like cell, the myofibroblast. The purpose of this paper is to review our understanding of the corneal keratocyte and the myofibroblast transformation process. Methods. These studies have been performed using tissues from primates, cats and rabbits under in vivo, in situ and in vitro conditions. Various types of injuries including radial keratotomy, lamellar keratectomy and full thickness corneal lacerations have been evaluated by in vivo confocal microscopy (CM) as well as conventional and laser confocal microscopic techniques. Results and Conclusions. The normal corneal stroma is populated by broad, flat cells that are inter-connected throughout the cornea by branching processes containing functional gap junctions (connexin 43). Injury leads to activatipn of keratocytes, synthesis of fibronectin, expression of α5β1 integrin and the migration of activated and functionally interconnected keratocytes. Once inside the wound, keratocytes begin to express smooth muscle specific α-actin (α-SM actin), characteristic of myofibroblasts, and develop a contractile apparatus comprised of intracellular α-SM microfilament bundles and extracellular fibronectin/collagen coupled by focal adhesions. 3-Dimensional and temporal studies indicate that myofibroblasts establish a 'shoe string-like' structure that contracts the wound by tightening of the interwoven network of cells. Recent studies indicate that the keratocyte to myofibroblast transformation is mediated by the cytokine, TGFβ1; TGFβ1 is a potent chemotactic factor for keratocytes; induces the expression α-SM actin, fibronectin and α5β1 integrin; and neutralizing antibodies to TGFβ block development of corneal fibrosis. The effect of TGFβ1 appears to be mediated by its initial effects on extracellular matrix and matrix receptor synthesis. Later, there is an 'outside-inside' signaling pathway mediated by the formation of focal adhesions and tyrosine phosphorylation of pp125FAK and p130 leading downstream to cell proliferation, α-SM actin expression and myofibroblast transformation.

Original languageEnglish (US)
Pages (from-to)S219
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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