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Human skin fibrosis: up‐regulation of collagen type III gene transcription in the fibrotic skin nodules of lower limb lymphoedema
Author(s) -
Karayi Arun Kumar,
Basavaraj Vijaya,
Narahari Saravu R.,
Aggithaya Madhur Guruprasad,
Ryan Terence J.,
Pilankatta Rajendra
Publication year - 2020
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/tmi.13359
Subject(s) - dermis , pathology , type i collagen , collagen, type i, alpha 1 , immunohistochemistry , skin biopsy , fibrosis , medicine , histopathology , biopsy , human skin , biology , extracellular matrix , genetics , microbiology and biotechnology
Abstract Objectives To investigate the cellular and molecular pathophysiology involved in the development of fibrotic skin of grade‐3 lymphoedema patients with a focus on collagen types. Methods Fibrotic and normal skin biopsy samples obtained from grade‐3 lymphoedema patients and normal individuals, respectively, were analysed by histopathology, quantitative real‐time PCR and immunohistochemistry to examine collagen gene expression. Results 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‐time PCR data showed significant ( P ‐value 0.0003) up‐regulation of Collagen type I and type III gene transcripts in the fibrotic skin of patients resulting in 38.94‐fold higher transcription of Collagen type III alpha‐1 gene than of Collagen type I alpha‐1 gene. Semi‐quantification of the per cent of haematoxylin‐DAB‐stained area of immunohistochemistry images also showed significant ( P < 0.0001) enhancement of both collagen proteins in the fibrotic skin of patients vs. normal human skin. Conclusions Gene transcript analysis revealed significant up‐regulation 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‐3 lymphoedema patients.