Scleroderma-like remodeling induced by type V collagen

Abstract

Recently, we discovered that New Zealand rabbits immunized with human type V collagen plus Freund's adjuvant present fibrosis and vasculitis of organs usually affected by systemic sclerosis. In this way, we studied the fibrillogenesis process to identify possible factors involved in altered remodeling observed in this scleroderma-like model. Additionally, we have done a very preliminary comparison with human skins obtained from scleroderma patients (n=3). Female New Zealand rabbits (n=10) were immunized subcutaneously with two doses of 1 mg collagen V (COL V) plus complete Freund's adjuvant for a 30-day interval, followed by two additional intramuscular booster immunizations in incomplete Freund's adjuvant for a 15-day interval. Animals from control group (n=10), were only inoculated with complete and incomplete Freund's adjuvant given at same conditions of COL V. Histological analysis of skins from animals and patients were done by Masson's trichrome staining, and immunofluorescence method to detect collagen fibers and interactions of types I, III and V collagen in the remodeling process. The analysis of animal skins showed collagen fibril deposits in the dermis after 7 days of sensibilization and an increase in these deposits after 75 and 120 days, respectively. Skin thickness and atrophy of sebaceous and sweat glands were progressively more intense in late sacrificed animals and correlated with increased amount of collagen deposition. Surprisingly, type V collagen was overexpressed both in animals and patients, forming dense and atypical collagen fibers in the dermis. We suggest that this anomalous expression of morphologically different type V collagen could justify the remodeling observed in scleroderma plaque.

Autoantibody profile in the experimental model of scleroderma induced by type V human collagen

“…The animals immunized with huCol V and killed at days 75 and 120 from immunization reproduced the previously described histological alterations [1][2][3][4][5] confirming the involvement of multiple organs: namely the skin, lungs, oesophagus, heart, synovia and kidneys, as in scleroderma. Animals injected with FCA or immunized with BSA did not show any histological complications.…”

“…1), and were in agreement with previously published histological results. [1][2][3][4][5] The FCA (n ¼ 10) and BSA (n ¼ 6) control animals did not develop anticollagen, RF, ANA or anti-Scl70 antibodies.…”

“…In this group we can include this new animal model for an autoimmune disease, induced in rabbits by their immunization with human type Collagen V (huCol V), recently described by Teodoro et al 1 in which the histological alterations are very similar to those of human scleroderma. [1][2][3][4][5] Scleroderma is a disease with an unknown etiology, characterized by vascular lesions and fibrosis in the skin and other organs because of the accumulation of proteins of the extracellular matrix. [6][7][8] Immunological abnormalities in SSc include activation of B and T lymphocytes, imbalance in cytokine profile and the production of a myriad of circulating autoantibodies.…”

Refractory remodeling of the microenvironment by abnormal type V collagen, apoptosis, and immune response in non-small cell lung cancer

“…In the normal lung, small amounts of collagen V are expressed as very thin fibrils in the basement membranes for binding with stromal collagen, this being important for cell adhesion and the matrix repair process [5]. In the current work, the decreased amount of fibers of collagens I, III, and V found in tumors was associated with low desmoplasia, probably due to a low co-polymerization among the fibers, thus resulting in a heterotypic assembly incapable of controlling fibril structure, collagen fibrillogenesis, and tumoral growth [5,25,26,28,29,40,41]. From the literature, data can be found showing an inverse correlation of the extent of the desmoplastic stroma reaction with the progression of carcinomas, which looks similar to the decrease of collagen V found in our study [2][3][4].…”

Collagen V-induced nasal tolerance downregulates pulmonary collagen mRNA gene and TGF-beta expression in experimental systemic sclerosis

“…This resulted in intense inflammation of the lung and progressive ECM remodeling of the septal and bronchovascular axis [11]. The examination of other organs usually affected in SSc, such as skin, esophagus, kidney, heart and synovial membrane, showed identical and intense ECM remodeling [12-14]. In addition, several immunological alterations were observed, such as the presence of types I, III and IV anti-collagen antibodies, circulating immune complexes, and the emergence of antinuclear antibodies (ANA) and anti-Scl-70 antibodies [15].…”