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Article type: Research Article
Authors: Mani, Haresh; | Sidhu, Gurmel S. | Kumari, Ranjana | Gaddipati, Jaya P. | Seth, Pankaj | Maheshwari, Radha K.
Affiliations: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA | Armed Forces Medical College, Pune, India
Note: [] Corresponding author: Radha K. Maheshwari, Ph.D., Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Tel.: +1 301 295 3394/3497; Fax: +1 301 295 1640; E-mail: [email protected]
Abstract: Wound healing is a highly ordered process, requiring complex and coordinated interactions involving peptide growth factors of which transforming growth factor-beta (TGF-β) is one of the most important. Nitric oxide is also an important factor in healing and its production is regulated by inducible nitric oxide synthase (iNOS). We have earlier shown that curcumin (diferuloylmethane), a natural product obtained from the plant Curcuma longa, enhances cutaneous wound healing in normal and diabetic rats. In this study, we have investigated the effect of curcumin treatment by topical application in dexamethasone-impaired cutaneous healing in a full thickness punch wound model in rats. We assessed healing in terms of histology, morphometry, and collagenization on the fourth and seventh days post-wounding and analyzed the regulation of TGF-β1, its receptors type I (tIrc) and type II (tIIrc) and iNOS. Curcumin significantly accelerated healing of wounds with or without dexamethasone treatment as revealed by a reduction in the wound width and gap length compared to controls. Curcumin treatment resulted in the enhanced expression of TGF-β1 and TGF-β tIIrc in both normal and impaired healing wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed an enhanced expression of TGF-β1 mRNA in curcumin treated wounds as evidenced by in situ hybridization. However, enhanced expression of TGF-β tIrc by curcumin treatment observed only in dexamethasone-impaired wounds at the 7th day post-wounding. iNOS levels were increased following curcumin treatment in unimpaired wounds, but not so in the dexamethasone-impaired wounds. The study indicates an enhancement in dexamethasone impaired wound repair by topical curcumin and its differential regulatory effect on TGF-β1, it's receptors and iNOS in this cutaneous wound-healing model.
Keywords: curcumin, wound healing, TGF-β1, TGF-β tIrc, TGF-β tIIrc, iNOS
Journal: BioFactors, vol. 16, no. 1-2, pp. 29-43, 2002
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