Collagen V alpha 1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure

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de Morais, Jymenez ; Velosa, Ana Paula P. ; Andrade, Priscila C. ; Frediani, Denise ; Carrasco, Solange ; Queiroz, Zelita A. de Jesus ; Martin, Patricia ; Saito, Renata F. ; Elias, Vitoria ; Goldenstein-Schainberg, Claudia ; Chammas, Roger ; Sampaio-Barros, Percival D. ; Capelozzi, Vera L. ; Teodoro, Walcy R.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 20, p. 14-pg., 2022-10-01.

Resumo

Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of alpha 1(V) and alpha 2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naive patients with SSc-related fibrosis and four healthy controls. Our data showed increased alpha 1(V) and alpha 2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the alpha 1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 +/- 1.34 vs. 66.84 +/- 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the alpha 1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the alpha 2(V) chain was overexpressed in the small vessels (63.18 +/- 3.56 vs. 12.16 +/- 0.81; p < 0.0001) and capillaries (60.88 +/- 5.82 vs. 15.11 +/- 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased alpha 1(V) chain expression. These results highlight an intense decrease in the alpha 1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the alpha 1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc. (AU)

• Processo FAPESP: 18/20403-6 - Marcadores biomoleculares de proliferação e remodelamento em doenças respiratórias agudas e crônicas: promissores alvos terapêuticos
• Beneficiário: Vera Luiza Capelozzi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/00415-0 - Caracterização do mecanismo celular e molecular em modelos pré-clínicos de esclerodermia induzidos pelo colágeno v
• Beneficiário: Walcy Paganelli Rosolia Teodoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/13220-5 - Efeito da indução de tolerância com peptídeos imunogênicos do colágeno tipo V na fibrose pulmonar associada à esclerose sistêmica experimental
• Beneficiário: Ana Paula Pereira Velosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular