{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:56:12Z","timestamp":1788188172517,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T00:00:00Z","timestamp":1577923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the cellular and molecular pathophysiology involved in the development of fibrotic skin of grade\u20103 lymphoedema patients with a focus on collagen types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fibrotic and normal skin biopsy samples obtained from grade\u20103 lymphoedema patients and normal individuals, respectively, were analysed by histopathology, quantitative real\u2010time PCR and immunohistochemistry to examine collagen gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Histopathologic analysis revealed epidermal changes such as orthokeratosis, hypergranulosis and irregular acanthosis in the skin biopsies. The thickened dermis contained nodules of haphazardly arranged thick collagen bundles. Real\u2010time PCR data showed significant (<jats:italic>P<\/jats:italic>\u2010value 0.0003) up\u2010regulation of Collagen type I and type III gene transcripts in the fibrotic skin of patients resulting in 38.94\u2010fold higher transcription of Collagen type III alpha\u20101 gene than of Collagen type I alpha\u20101 gene. Semi\u2010quantification of the per cent of haematoxylin\u2010DAB\u2010stained area of immunohistochemistry images also showed significant (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) enhancement of both collagen proteins in the fibrotic skin of patients vs. normal human skin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gene transcript analysis revealed significant up\u2010regulation of Collagen type III vs. Collagen type I in fibrotic skin of limb nodules from patient biopsies. Histopathological and immunohistochemical analysis also revealed enhancement of Collagen types I and III in fibrotic vs. normal skin. The findings of this preliminary study indicate the potentially significant involvement of Collagen type III in the development of the fibrotic skin of grade\u20103 lymphoedema patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tmi.13359","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T15:06:03Z","timestamp":1575903963000},"page":"319-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Human skin fibrosis: up\u2010regulation of collagen type III gene transcription in the fibrotic skin nodules of lower limb lymphoedema"],"prefix":"10.1111","volume":"25","author":[{"given":"Arun Kumar","family":"Karayi","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Central University of Kerala Kasaragod India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya","family":"Basavaraj","sequence":"additional","affiliation":[{"name":"Department of Pathology JSS Medical College &amp; 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