1. ¹Center for Metabolic Biology, College of Liberal Arts and Sciences, Arizona State University, Tempe, Arizona, USA
2. ²Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona, USA
3. ³Department of Biology, Scottsdale Community College, Scottsdale, Arizona, USA
4. ⁴Department of Surgery, Stanford University, Stanford, California, USA
5. ⁵Palo Alto VA Health Care System, Palo Alto, California, USA
6. ⁶Weldon School of Biomedical Engineering, Purdue University, Purdue, Indiana, USA

Correspondence: Dr Colleen M. Brophy, Division of Vascular Surgery Vanderbilt University Medical Center 161 21st Ave. S. D-5237 MCN Nashville, TN 37232-2735. E-mail: colleen.brophy@vanderbilt.edu

Received 30 March 2008; Revised 25 May 2008; Accepted 30 June 2008; Published online 11 September 2008.

Abstract

A growing body of evidence suggests the involvement of connective tissue growth factor (CTGF) in the development and maintenance of fibrosis and excessive scarring. As the expression of this protein requires an intact actin cytoskeleton, disruption of the cytoskeleton represents an attractive strategy to decrease CTGF expression and, consequently, excessive scarring. The small heat-shock-related protein (HSP20), when phosphorylated by cyclic nucleotide signaling cascades, displaces phospho-cofilin from the 14-3-3 scaffolding protein leading to activation of cofilin as an actin-depolymerizing protein. In the present study, we evaluated the effect of AZX100, a phosphopeptide analogue of HSP20, on transforming growth factor--1 (TGF-1)-induced CTGF and collagen expression in human keloid fibroblasts. We also examined the effect of AZX100 on scar formation in vivo in dermal wounds in a Siberian hamster model. AZX100 decreased the expression of CTGF and type I collagen induced by TGF-1, endothelin, and lysophosphatidic acid. Treatment with AZX100 decreased stress fiber formation and altered the morphology of human dermal keloid fibroblasts. In vivo, AZX100 significantly improved collagen organization in a Siberian hamster scarring model. Taken together, these results suggest the potential use of AZX100 as a strategy to prevent excessive scarring and fibrotic disorders.