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Mitogen-Activated Protein Kinase p38 Pathway in Venous Ulcer Fibroblasts

Boston University School of Medicine, joseph.raffetto{at}med.va.gov

Christopher H. Gram, MD

Vascular Surgery, Boston VA Healthcare System Boston, Massachusetts

Kristen C. Overman, BS

Surgical Specialists, Decatur, Illinois

James O. Menzoian, MD

University of Connecticut, Farmington, Connecticut

Objective: Venous ulcer fibroblasts (w-fb) have attenuated growth compared to normal fibroblasts (n-fb). The MAPKp38 pathway mediates stress-responses in various diseases. We hypothesize that p38 pathway is altered in w-fb. Methods: W-fb were isolated from venous ulcers and n-fb from the ipsilateral thigh. Fibroblasts were analyzed for phosphorylated p38 using immunoblot. The relation between p38 and w-fb proliferation was assessed with SB203580 (p38 inhibitor). Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed. Results: Phosphorylated p38 expression was increased in w-fb (AU%=233.5±59.7, P=0.039) compared to n-fb (AU%=99.9±14.6). W-fb treated with SB203580 demonstrated increased growth compared to untreated w-fb. W-fb treated with bFGF demonstrated decreased p38. TNF- and IL-1β significantly increase p38 expression. Conclusions: MAPK p38 is up-regulated in w-fb. Regulation of w-fb proliferation is influenced by p38. Altering the p38 pathway in vivo with growth factors or cytokine inhibition may improve fibroblast proliferation and venous ulcer healing.

Key Words: fibroblasts • venous ulcer • growth factors • senescence • cell proliferation • mitogen-activated protein kinase • MAPK p38 • kinase inhibitor • SB203580

This version was published on August 1, 2008

Vascular and Endovascular Surgery, Vol. 42, No. 4, 367-374 (2008)
DOI: 10.1177/1538574408316140


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