title: Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide synthase during impaired wound healing.
abstract: Wound healing is a highly ordered process, requiring complex and coordinated interactions involving peptide growth factors of which transforming growth factor-beta (TGF-beta) 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-beta1, 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-beta1 and TGF-beta tIIrc in both normal and impaired healing wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed an enhanced expression of TGF-beta1 mRNA in curcumin treated wounds as evidenced by in situ hybridization. However, enhanced expression of TGF-beta 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-beta1, it's receptors and iNOS in this cutaneous wound-healing model.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Haresh
authors.initials: H
authors.lastname: Mani
authors.forename: Gurmel S
authors.initials: GS
authors.lastname: Sidhu
authors.forename: Ranjana
authors.initials: R
authors.lastname: Kumari
authors.forename: Jaya P
authors.initials: JP
authors.lastname: Gaddipati
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.forename: Radha K
authors.initials: RK
authors.lastname: Maheshwari
mesh_terms: D030201:Activin Receptors, Type I / Q000032:analysis; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000737:chemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; D003474:Curcumin