Animal models in systemic sclerosis: an update

Abstract

Purpose of review Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by early inflammation followed by excessive fibrosis in the skin and internal organs. Enhancing our comprehension of SSc pathogenesis is essential to develop effective therapeutic strategies. Animal models that mimic one or more aspects of SSc have been proven to be a valuable resource for investigating disease mechanisms. This review aims to provide an updated overview of the existing SSc animal models and the potentially relevant pathways to SSc pathogenesis. Recent findings This review focuses on the most recently generated and investigated animal models, which delve into novel pathways beyond existing models or employ genetic technologies to gain a deeper understanding of SSc pathogenesis including activation of early type I interferon (IFN) signaling pathway, immune cell function and pulmonary artery hypertension (PAH). Summary While no single animal model can fully replicate SSc, a combination of different models can offer valuable insights into the pathways involved in the onset and advancement of the SSc. These insights can prove animal models as a crutial preclinical tool for developing effective treatments for SSc.

Recent Insights into Cellular and Molecular Mechanisms of Defective Angiogenesis in Systemic Sclerosis

“…All the animal models developed for SSc display a fibrotic phenotype, but only a few of them are able to reproduce EC dysfunction and defective angiogenesis [ 81 ].…”

“…Tumor necrosis factor ( TNF )-transgenic mice carry a modified human TNF transgene in which the 3′-region of the TNF gene has been replaced with that of the human β-globin gene [ 81 , 95 ]. The TNF -transgenic mice have been proposed as a novel animal model of SSc-PAH, as they display a pulmonary vasculopathy characterized by collagen deposition in the wall of small arteries/arterioles and vascular occlusion, and their lungs show signs of EndoMT and dysregulated angiogenic pathways [ 81 , 95 ].…”

“…This animal model, obtained by transplanting spleen cells from B10.D2 donor mice into lethally irradiated Rag-2 KO Balb/c mice, was found to display fibroproliferative vasculopathy, with ET-1 up-regulation in the perivascular area and a reduction in the vascular lumen [ 81 , 96 ].…”

“…Type V Collagen Immunized Mouse EC activation and apoptosis [97] Rats Subcutaneously Injected with NaClO Capillary disruption, narrowing of vascular lumen, and perivascular infiltration in lungs [98] TNF-Transgenic Mouse Pulmonary vasculopathy; EndoMT; dysregulated angiogenic pathways [81,95] Sclerodermatous Graft-Versus-Host Disease Mouse Fibroproliferative vasculopathy [81,96] EC, endothelial cell; EndoMT, endothelial-to-mesenchymal transition; PAH, pulmonary arterial hypertension; SSc, systemic sclerosis.…”