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Plast Reconstr Surg. 2011 Nov;128(5):451e-459e. doi: 10.1097/PRS.0b013e31822b65c7.

An activin receptor-like kinase 5 inhibitor reduces collagen deposition in a rat dermal incision wound healing model.

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1
Pfizer Worldwide Research and Development, Pfizer, Inc., Groton, CT 06340, USA. bianf48103@yahoo.com

Abstract

BACKGROUND:

Excessive dermal scarring is characterized by an overabundant deposition of extracellular matrix caused by fibrosis. The purpose of this study was to modify a rodent model of cutaneous healing for use in the development of compounds to minimize scarring, and to test the model with a small molecule inhibitor of transforming growth factor-β type I receptor, activin receptor-like kinase 5, because this class of inhibitors has been demonstrated to be effective in minimizing fibrosis in other organs.

METHODS:

The rodent model of cutaneous healing consists of uniform full-thickness incisional dermal wounds in rats. Wounds were allowed to heal by secondary intention, generally over a 14-day period. The usefulness of the model was tested by the application of an activin receptor-like kinase 5 inhibitor, CP-639180. Activin receptor-like kinase 5 inhibition antagonizes the transforming growth factor-β pathway, and was used to determine whether there was an effect on collagen deposition in wounds. The compound was applied once per day for 7 days starting at postwounding day 0 or 7 (early or late treatment regimens). Wounds were analyzed histologically for collagen deposition and biochemically for quantification of collagen changes.

RESULTS:

Early and late treatment regimens with the activin receptor-like kinase 5 inhibitor significantly reduced collagen deposition without impairing wound healing.

CONCLUSIONS:

Application of a small molecular inhibitor of activin receptor-like kinase 5 appears to significantly reduce collagen deposition in rat dermal wounds as reported here for the first time. Activin receptor-like kinase 5 inhibition may offer a novel approach to reducing proliferative scars in humans because collagen accumulation is a core event in scarring.

PMID:
22030504
DOI:
10.1097/PRS.0b013e31822b65c7
[Indexed for MEDLINE]
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