Adv Wound Care (New Rochelle) 3(12): 751-761

Differential Apoptosis in Mucosal and Dermal Wound Healing

^{Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois.}

^{Department of Oral Sciences, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois.}

^{Correspondence: Center for Wound Healing and Tissue Regeneration (MC 859), College of Dentistry, University of Illinois at Chicago, 801 S. Paulina–Room 401B, Chicago, IL 60612-7211 (e-mail:}ude.ciu@teipidl).

Received 2013 Feb 11

Abstract

Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing.

Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds.

Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; p<0.05), Casp7 (at D5; p<0.05), Trp53 (at 24 h and D5; p<0.05), Tnfrsf1b (at 24 h; p<0.05), FasR (at 24 h, D5, and D7; p<0.05), and Casp8 (at 24 h; p<0.05) and significantly lower gene expression of Tradd (at 24 h; p<0.05).

Innovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin.

Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing.

Abstract

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Luisa Ann DiPietro, DDS, PhD

Key Findings

Abbreviations and Acronyms

ANOVA	analysis of variance
Apaf1	apoptotic peptidase activating factor 1
Bax	BCL2-associated X protein
Bcl-2	B-cell CLL/lymphoma 2
Casp	caspase
Cycs	cytochrome C
DR	death receptors
Fadd	Fas associated death domain
FasR	TNF receptor superfamily member 6
RQ	relative quantity
RT-PCR	reverse transcriptase–polymerase chain reaction
TGF	transforming growth factor
Tnfrsf1b	tumor necrosis factor receptor gene super family 1b
TNF-α	tumor necrosis factor alpha
Tradd	TNFRSF1A-associated death domain
Trp53	transformation related protein 53
UV	ultraviolet
VEGF	vascular endothelial growth factor

Abbreviations and Acronyms

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