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AuthorAbd El-Aleem, Seham A
AuthorMohammed, Hanaa Hassanein
AuthorSaber, Entesar Ali
AuthorEmbaby, Azza S
AuthorDjouhri, Laiche
Available date2020-06-21T05:45:31Z
Publication Date2020-06-01
Publication NameBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Identifierhttp://dx.doi.org/10.1016/j.bbadis.2020.165850
CitationAbd El-Aleem SA, Mohammed HH, Saber EA, Embaby AS, Djouhri L. Mutual inter-regulation between iNOS and TGF-β1: Possible molecular and cellular mechanisms of iNOS in wound healing [published online ahead of print, 2020 Jun 1]. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165850. doi:10.1016/j.bbadis.2020.165850
ISSN0925-4439
URIhttp://hdl.handle.net/10576/15075
AbstractAbnormal wound healing with excessive scarring is a major health problem with socioeconomic and psychological impacts. In human, chronic wounds and scarring are associated with upregulation of the inducible nitric oxide synthase (iNOS). Recently, we have shown physiological regulation of iNOS in wound healing. Here, we sought to investigate the possible mechanistic role of iNOS in wound healing using biochemical and immunohistochemical assays. We found: (a) iNOS is the main source of wound nitric oxide (NO), (b) NOS inhibition in the wound, downregulated iNOS protein, mRNA and enzymatic activity, and reduced wound NO, and (c) iNOS inhibition resulted in delayed healing at early time points, and excessive scarring at late time points. Furthermore, molecular and cellular analysis of the wound showed that iNOS inhibition significantly (P < 0.05) increased TGF-β1 mRNA and protein levels, fibroblasts and collagen deposition. These latter findings suggest that iNOS might be exerting its action in the wound by signaling through TGF-β1 that activates wound fibroblasts to produce excessive collagen. Our current findings provide further support that iNOS is crucial for physiological wound healing, and suggest that dysregulation of iNOS during the inflammatory phase impairs healing, and results in disfiguring post-healing scarring. Thus, the mutual feedback regulation between iNOS and TGF-β1 at the gene, protein and functional levels might be the mechanism through which iNOS regulates the healing. Monitoring and maintenance of wound NO levels might be important for healing and avoiding long-term complications in susceptible people including patients with diabetic wounds, venous ulcers or keloid prone.
Languageen
PublisherElsevier
SubjectAminoguanidine
Arginase
Inflammation
L-NAME
Nitric oxide synthase
Scarring
TGF-β1
Wound healing
TitleMutual inter-regulation between iNOS and TGF-β1: Possible molecular and cellular mechanisms of iNOS in wound healing.
TypeArticle
Issue Number10
Volume Number1866


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