Possible association of elevated serum collagen type IV level with skin sclerosis in systemic sclerosis

Abstract

Collagen type IV is the primary collagen in the basement membranes around blood vessels and in the dermoepidermal junction in the skin. Perivascular collagen type IV is synthesized by endothelial cells and pericytes, and contributes to the homeostasis and remodeling of blood vessels. It has been well recognized that elevated serum collagen type IV levels are associated with the liver fibrosis. The objective was to examine serum collagen type IV levels and their clinical associations in patients with systemic sclerosis (SSc), and to examine the expression of collagen type IV in the fibrotic skin in SSc. Serum collagen type IV levels in SSc patients and diffuse cutaneous type SSc patients were significantly higher than those in healthy individuals. Serum collagen type IV levels were positively correlated with modified Rodnan total skin score. Serum collagen type IV levels in early stage (disease duration ≤3 years) diffuse cutaneous SSc patients were significantly elevated. Serum collagen type IV levels in SSc patients with digital ulcers (DU) were significantly elevated. In immunohistochemical staining, the expression of collagen type IV around dermal small vessels in the affected skin was reduced compared with those of normal individuals. These results suggest that elevated serum collagen type IV levels may be associated with the skin sclerosis in the early stage of SSc. The measurement of serum collagen type IV levels in SSc patients may be useful as a disease activity marker in skin sclerosis and DU.

Type III, IV, and VI Collagens Turnover in Systemic Sclerosis – a Longitudinal Study

“…As vascular damage is found in both lcSSc and dcSSc, it might explain the increase of type IV collagen turnover in both lcSSc and dcSSc compared to controls. Type IV collagen has previously been shown upregulated in SSc by Motegi and colleagues 23 . They found that type IV collagen was elevated in patients with three years of disease duration or less.…”

Suppressive Regulation by MFG‐E8 of Latent Transforming Growth Factor β–Induced Fibrosis via Binding to αv Integrin: Significance in the Pathogenesis of Fibrosis in Systemic Sclerosis

“…It has been suggested that vasculopathy and dysfunction of ECs might be associated with the development of skin fibrosis in SSc patients . Additionally, it has been reported that numbers of pericytes/VSMCs in all types of blood vessels in lesional skin are decreased in SSc patients . Collectively, vasculopathy‐induced dysfunction of and reduction in ECs and pericytes/VSMCs might be associated with decreased expression of MFG‐E8 in lesional skin of SSc patients.…”

Integrated analysis of dermal blister fluid proteomics and genome-wide skin gene expression in systemic sclerosis: an observational study

“…COL4A1 is synthesised by endothelial cells and pericytes and its primary function is in angiogenesis. 18 COL4A1 has an established role in other fibrotic diseases including liver fibrosis, Goodpasture's syndrome, and Alport syndrome. Mouse models relevant to systemic sclerosis, have confirmed increased gene expression of COL4A1 in the skin and lung.…”