| Full text | |
| Author(s): Show less - |
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.
Total Authors: 14
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 20, p. 14-pg., 2022-10-01. |
| Abstract | |
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) | |
| FAPESP's process: | 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets |
| Grantee: | Vera Luiza Capelozzi |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/00415-0 - CHARACTERIZATION OF CELLULAR AND MOLECULAR MECHANISM IN PRE-CLINICAL MODELS OF SCLERODERMA INDUCED BY COLLAGEN V |
| Grantee: | Walcy Paganelli Rosolia Teodoro |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/13220-5 - Effect of induction of tolerance with immunogenic peptides of collagen type V on pulmonary fibrosis associated with experimental systemic sclerosis |
| Grantee: | Ana Paula Pereira Velosa |
| Support Opportunities: | Regular Research Grants |