Enhanced biosynthesis of extracellular matrix proteins and TGF-beta 1 by polyinosinic-polycytidylic acid during cutaneous wound healing in vivo.
In our previous study, we have shown that polyinosinic-polycytidylic acid (poly I:C), a double-stranded RNA, and a potent inducer of interferon, enhanced the wound healing in rats and mice. Increased levels of laminin and collagen, and greater influx of dermal fibroblasts were observed in poly I:C-treated wounds as compared to untreated wounds (Bhartiya et al., 1992, J. Cell. Physiol., 150:312-319). In this study, we have explored the mechanism of enhanced wound healing by poly I:C in rats. Poly I:C (1 mg/kg) in phosphate buffered saline was injected intraperitoneally 18 h prior to wound healing, and the animals were sacrificed on day 3 postwounding. Immunofluorescence studies showed increased expression of adhesion molecules that includes ICAM-1 (intercellular adhesion molecule-1;CD54) and VCAM-1 (vascular cell adhesion molecule; CD 106) in poly I:C-treated wounds as compared to untreated control. Poly I:C treatment resulted in an increase in the mRNA levels of collagen type 1 (alpha), collagen III, laminin B1, and transforming growth factor-beta 1(TGF-beta 1) in wounds compared to untreated wounds as demonstrated by in situ hybridization and PCR analysis. These studies suggests that poly I:C upregulates the biosynthesis of adhesion molecules, extracellular matrix proteins (ECM), and TGF-beta 1 in the wound bed. Adhesion molecules and ECM play a major role in wound healing, and TGF-beta 1 has been known to be a potent wound healer. Therefore, the increased expression of these molecules may play a role in the enhanced healing by poly I:C observed in rats.
Sidhu
G S
GS
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Thaloor
D
D
Singh
A K
AK
Raghunath
P N
PN
Maheshwari
R K
RK
D000818:Animals; D003094:Collagen / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D019085:Fluorescent Antibody Technique, Direct; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007797:Laminin / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011070:Poly I-C / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000293:injuries*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D007797:Laminin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen; D011070:Poly I-C