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Article

Collagen V α1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure

by
Jymenez de Morais
1,
Ana Paula P. Velosa
1,
Priscila C. Andrade
2,
Denise Frediani
3,
Solange Carrasco
1,
Zelita A. de Jesus Queiroz
1,
Patrícia Martin
1,
Renata F. Saito
4,5,
Vitória Elias
1,
Cláudia Goldenstein-Schainberg
1,
Roger Chammas
4,5,
Percival D. Sampaio-Barros
1,
Vera L. Capelozzi
2 and
Walcy R. Teodoro
1,*
1
Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil
2
Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil
3
Discipline of Clinical Emergency (LIM 51), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil
4
Center for Translational Research in Oncology (LIM24), Department of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil
5
Instituto do Câncer do Estado de São Paulo, São Paulo 01246-903, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(20), 12654; https://doi.org/10.3390/ijms232012654
Submission received: 31 August 2022 / Revised: 6 October 2022 / Accepted: 14 October 2022 / Published: 21 October 2022
(This article belongs to the Special Issue Updates & New Concepts in Collagen)
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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 α1(V) and α2(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-naïve patients with SSc-related fibrosis and four healthy controls. Our data showed increased α1(V) and α2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the α1(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 α1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the α2(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 α1(V) chain expression. These results highlight an intense decrease in the α1(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 α1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.
Keywords: collagen V alpha chains; skin; systemic sclerosis; papillary dermis; fibrosis collagen V alpha chains; skin; systemic sclerosis; papillary dermis; fibrosis

Share and Cite

MDPI and ACS Style

de Morais, J.; Velosa, A.P.P.; Andrade, P.C.; Frediani, D.; Carrasco, S.; Queiroz, Z.A.d.J.; Martin, P.; Saito, R.F.; Elias, V.; Goldenstein-Schainberg, C.; et al. Collagen V α1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure. Int. J. Mol. Sci. 2022, 23, 12654. https://doi.org/10.3390/ijms232012654

AMA Style

de Morais J, Velosa APP, Andrade PC, Frediani D, Carrasco S, Queiroz ZAdJ, Martin P, Saito RF, Elias V, Goldenstein-Schainberg C, et al. Collagen V α1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure. International Journal of Molecular Sciences. 2022; 23(20):12654. https://doi.org/10.3390/ijms232012654

Chicago/Turabian Style

de Morais, Jymenez, Ana Paula P. Velosa, Priscila C. Andrade, Denise Frediani, Solange Carrasco, Zelita A. de Jesus Queiroz, Patrícia Martin, Renata F. Saito, Vitória Elias, Cláudia Goldenstein-Schainberg, and et al. 2022. "Collagen V α1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure" International Journal of Molecular Sciences 23, no. 20: 12654. https://doi.org/10.3390/ijms232012654

APA Style

de Morais, J., Velosa, A. P. P., Andrade, P. C., Frediani, D., Carrasco, S., Queiroz, Z. A. d. J., Martin, P., Saito, R. F., Elias, V., Goldenstein-Schainberg, C., Chammas, R., Sampaio-Barros, P. D., Capelozzi, V. L., & Teodoro, W. R. (2022). Collagen V α1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure. International Journal of Molecular Sciences, 23(20), 12654. https://doi.org/10.3390/ijms232012654

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