Dr. Leask owns stock in FibroGen.
Brief Report: Fibrosis Caused by Loss of PTEN Expression in Mouse Fibroblasts Is Crucially Dependent on CCN2
Article first published online: 28 OCT 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 11, pages 2940–2944, November 2013
How to Cite
Liu, S., Parapuram, S. K. and Leask, A. (2013), Brief Report: Fibrosis Caused by Loss of PTEN Expression in Mouse Fibroblasts Is Crucially Dependent on CCN2. Arthritis & Rheumatism, 65: 2940–2944. doi: 10.1002/art.38121
- Issue published online: 28 OCT 2013
- Article first published online: 28 OCT 2013
- Accepted manuscript online: 27 AUG 2013 03:29PM EST
- Manuscript Accepted: 1 AUG 2013
- Manuscript Received: 5 APR 2013
- Canadian Scleroderma Research Group
- Canadian Institutes of Health Research
- Scleroderma Society of Ontario
Protein phosphatase and tensin homolog (PTEN) expression is reduced in dermal fibroblasts isolated from patients with diffuse cutaneous systemic sclerosis, a fibrotic autoimmune disease. In support of this finding, deletion of the PTEN gene in the dermal fibroblasts of mice has been shown to result in skin fibrosis and in vivo overexpression of connective tissue growth factor (CTGF; CCN2), a proadhesive matricellular protein; however, whether CCN2 is required for the fibrosis caused by loss of PTEN is unclear. This study was undertaken to investigate the role of CCN2 in fibrosis caused by reduced PTEN expression.
We generated conditional knockout mice in which PTEN was deleted in fibroblasts, either alone or in combination with CCN2. Skin samples were collected for histologic examination, immunohistochemical analysis, and collagen assay.
Loss of CCN2 resulted in resistance to the increases in collagen production and myofibroblast recruitment that are caused by loss of PTEN. CCN2 deficiency did not impair Akt phosphorylation or the increases in the intensity of proliferating cell nuclear antigen staining that were caused by loss of PTEN.
These data are consistent with the notion that CCN2 is required for particular aspects of the fibroproliferative response; therapeutic strategies blocking CCN2 may be of clinical benefit in combating fibrotic disease.