Detection of V, III and I type collagens of dermal tissues in skin lesions of patients with systemic sclerosis and its implication

Abstract

This study investigated the contents and distribution of collagen V (Col V) in skin lesions of the patients with systemic sclerosis (SSc) and its roles in the pathogenesis. The contents and distribution for α1 chain of collagen type I, III and V [α1 (I), α1 (III) and α1 (V)] in skin lesions of 36 patients with SSc (9 cases of mild fibrosis, 14 moderate, and 13 severe) were detected by using immunohistochemical SP method. Six cases of normal skin tissues served as controls. The results showed that there was diffuse distribution for three kinds of collagens in dermis. The deep staining α1 (I) and α1 (III) masses or bands were seen in reticular layer, while α1 (V) was distributed more homogeneously. From control to weak, moderate and severe fibrosis stages, α1 (I), α1 (III) and α1 (V) showed a gradually increased trend in skin lesions (P<0.05). α1 (V) was obviously elevated in skin lesions at early stage and persisted in whole fibrotic process and risen in greater contents, while α1 (I) and α1 (III) were to go higher late and were apparently elevated at moderate and late stages. Compared with α1 (I), α1 (V) took leading increase at early stage in skin lesions (P<0.01), and had more elevated contents than α1 (III) at moderate and late stages. The fibrotic changes in dermal reticular layer occurred earlier than those in papillary layer, and the abnormalities of α1 (V)/α1 (I) ratio appeared before α1 (III)/α1 (I) ratio. It was concluded that a lot of α1 (V) began to deposit in greater contents prior to α1 (I) and α1 (III) at early stage in SSc and persisted in whole fibrotic process. The changes of α1 (V) contents in reticular layer occurred earlier than those in papillary layer, and it suggested that the fibrosis in reticular layer appeared earlier.

Keywords

sclerosis, systemic / V type collagen / immunohistochemical staining

References

[1] VargaJ., AbrahamD.. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest, 2007, 117(3): 557-567

[2] RuzekM. C., JhaS., LedbetterS., et al.. A modified model of graft-versus-host-induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease. Arthritis Rheum, 2004, 50(4): 1319-1331

[3] RouletM., RuggieroF., KarsentyG., et al.. A comprehensive study of the spatial and temporal expression of the col5a1 gene in mouse embryos: a clue for understanding collagen V function in developing connective tissues. Cell Tissue Res, 2007, 327(2): 323-332

[4] VelosaA. P. P., TeodoroW. R., de OliveiraC. C., et al.. Collagen V nasal tolerance in experimental model of systemic sclerosis. Arch Dermatol Res, 2007, 299(4): 177-189

[5] Subcommittee for scleroderma criteria of the American Rheumatism Association DiagnosticTherapeutic Criteria Committee.. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum, 1980, 23(5): 581-590

[6] BezerraM. C., TeodoroW. R., de OliveiraC. C., et al.. Scleroderma-like remodeling induced by type V collagen. Arch Dermatol Res, 2006, 298(2): 51-57

[7] VerrecchiaF., LaboureauJ., VerolaO., et al.. Skin involvement in scleroderma—where histological and clinical scores meet. Rheumatology (Oxford), 2007, 46(5): 33-841

[8] KahaiS., VaryC. P. H., GaoY., et al.. Collagen, type V, alpha1 (COL5A1) is regulated by TGF-beta in osteoblasts. Matrix Biol, 2004, 23(7): 445-455

[9] YoshidaS., HaqueA., MizobuchiT., et al.. Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants. Am J Transplant, 2006, 6(4): 724-735

[10] SumpterT. L., WilkesD. S.. Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection. Am J Physiol Lung Cell Mol Physiol, 2004, 286(6): 1129-1139

[11] LuparelloC., SirchiaR.. Type V collagen regulates the expression of apoptotic and stress response genes by breast cancer cells. J Cell Physiol, 2005, 202(2): 411-421

[12] RothblumK., StahlR. C., CareyD. J.. Constitutive release of alpha 4 type V collagen N-terminal domain by Schwann cells and binding to cell surface and extracellular matrix heparan sulfate proteoglycans. J Biol Chem, 2004, 279(49): 51 282-51 288

[13] Chanut-DelalandeH., Bonod-BidaudC., CogneS., et al.. Development of a functional skin matrix requires deposition of collagen V heterotrimers. Mol Cell Biol, 2004, 24(13): 6049-6057

[14] WenstrupR. J., FlorerJ. B., BrunskillE. W., et al.. Type V collagen controls the initiation of collagen fibril assembly. J Biol Chem, 2004, 279(51): 53 331-53 337

[15] WenstrupR. J., FlorerJ. B., DavidsonJ. M., et al.. Murine model of the Ehlers-Danlos syndrome. col5α1 haploin-sufficiency disrupts collagen fibril assembly at multiple stages. J Biol Chem, 2006, 281(18): 12 888-12 895

[16] ParraE. R., TeodoroW. R., VelosaA. P. P., et al.. Interstitial and vascular type V collagen morphologic disorganization in usual interstitial pneumonia. J Histochem Cytochem, 2006, 54(12): 1315-1325

[17] LaplanteP., RaymondM. A., GagnonG., et al.. Novel fibrogenic pathways are activated in response to endothelial apoptosis: implications in the pathophysiology of systemic sclerosis. J Immunol, 2005, 174(9): 5740-5749