Co-upregulation of Transforming Growth Factor Beta-1 and Nitric Oxide Synthase in Keloid by comparison to normal human skin-A possible role for TGFβ1 and NOS in pathogenesis of keloid

Abstract

Keloid disease is a benign but progressive form of abnormal wound healing associated with skin fibrosis and can cause a major functional disability and morbidity. TGF beta (TGFβ) and Nitric Oxide (NO) are active biomarkers known to regulate phases of wound healing and have been implicated in pathogenesis of fibrotic disease. There are three isoforms of TGFβ (1, 2 and 3) TGFβ1 and 3 have a crucial role in fibrosis, with TGFβ1 profibrotic and TGFβ3 antifibrotic. NO is produced by Nitric Oxide Synthase (NOS) which exist in three isoforms, inducible NOS (iNOS), endothelial NOS (ecNOS) and neuronal NOS (nNOS). TGFβ isoforms and NO were found to be associated with fibrotic disorders affecting the skin. We hypothesis that the interaction between TGFβ and NO in keloid could promote the excessive collagen deposition associated with this disorder.Using immunohistochemistry, we investigated the profile of TGFβ isoforms (TGFβ1, 3) and NOS isoforms (iNOS and ecNOS) in keloid tissues and normal human skin. The cellular distribution of all the isoforms were studied and the protein levels were assessed by using H-Scoring and Image J Scoring systems.

Cellular and physiological upregulation of inducible nitric oxide synthase, arginase, and inducible cyclooxygenase in wound healing

“…Wound repair normally involves iNOS, arginase, and COX‐2 and it is likely that interference with these physiological responses to injury either by inhibitors or inducers of these enzymes could alter the healing process. However delayed healing which occurs under conditions associated with low expression for example, in malnutrition and diabetes (Schaffer, Tantry, Ahrendt, Wasserkrug, & Barbul, ; Schäffer, Tantry, van Wesep, & Barbul, ) or excessive upregulation of these enzymes such as in chronic wounds (S. Abd El‐Aleem et al, ; Seham A. Abd El‐Aleem et al, ; Abd El‐Aleem et al, ; Jude et al, ) might be treated using specific inducers or inhibitors.…”

“…Wound repair is regulated by a number of chemical factors such as cytokines, nitric oxide (NO), and prostaglandins (Chang, Liao, & Kuo, ; Dzik, ; Gonzalez et al, ; Tomlinson & Willoughby, ). Previously we have shown that dysregulation of these mediators contributes to abnormal wound healing causing chronicity of the wound (S. Abd El‐Aleem, Muftah, & Jude, ; Abd El‐Aleem et al, ; Jude, Boulton, Ferguson, & Appleton, ) or excessive fibrosis as in keloid (S. Abd El‐Aleem, Abdelwahab, & Osman, ).…”

Opinion on Different Findings in Experimental and Clinical Medicine

“…In keloid, above all a co-upregulation of TGFß1 and inducible nitric oxide synthase was found. This research article is of great importance, because it gives the possibility to develop a specific antifibrotic pharmacological agent [5].…”