Calpain activity is essential in skin wound healing and contributes to scar formation

Nassar, Dany, Letavernier, Emmanuel, Baud, Laurent, Aractingi, Selim and Khosrotehrani, Kiarash (2012) Calpain activity is essential in skin wound healing and contributes to scar formation. PLoS One, 7 5: e37084.1-e37084.10. doi:10.1371/journal.pone.0037084

Author Nassar, Dany
Letavernier, Emmanuel
Baud, Laurent
Aractingi, Selim
Khosrotehrani, Kiarash
Total Author Count Override 5
Title Calpain activity is essential in skin wound healing and contributes to scar formation
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-05
Sub-type Article (original research)
DOI 10.1371/journal.pone.0037084
Open Access Status DOI
Volume 7
Issue 5
Start page e37084.1
End page e37084.10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Wound healing is a multistep phenomenon that relies on complex interactions between various cell types. Calpains are ubiquitously expressed proteases regulating several processes including cellular adhesion and motility as well as inflammation and angiogenesis. Calpains can be targeted by inhibitors, and their inhibition was shown to reduce organ damage in various disease models. We aimed to assess the role of calpains in skin healing and the potential benefit of calpain inhibition on scar formation. We used a pertinent model where calpain activity is inhibited only in lesional organs, namely transgenic mice overexpressing calpastatin (CPST), a specific natural calpain inhibitor. CPST mice showed a striking delay in wound healing particularly in the initial steps compared to wild types (WT). CPST wounds displayed reduced proliferation in the epidermis and delayed re-epithelization. Granulation tissue formation was impaired in CPST mice, with a reduction in CD45+ leukocyte infiltrate and in CD31+ blood vessel density. Interestingly, wounds on WT skin grafted on CPST mice (WT/CPST) showed a similar delayed healing with reduced angiogenesis and inflammation compared to wounds on WT/WT mice demonstrating the implication of calpain activity in distant extra-cutaneous cells during wound healing. CPST wounds showed a reduction in alpha-smooth muscle actin (αSMA) expressing myofibroblasts as well as αSMA RNA expression suggesting a defect in granulation tissue contraction. At later stages of skin healing, calpain inhibition proved beneficial by reducing collagen production and wound fibrosis. In vitro, human fibroblasts exposed to calpeptin, a pan-calpain inhibitor, showed reduced collagen synthesis, impaired TGFβ-induced differentiation into αSMA-expressing myofibroblasts, and were less efficient in a collagen gel contraction assay. In conclusion, calpains are major players in granulation tissue formation. In view of their specific effects on fibroblasts a late inhibition of calpains should be considered for scar reduction.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e37084

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Thu, 04 Oct 2012, 09:53:47 EST by Roheen Gill on behalf of UQ Centre for Clinical Research