Abstract | INTRODUCTION: Scleroderma, or systemic sclerosis, is a complex connective tissue disorder characterized by autoimmunity, vasculopathy, and progressive fibrosis of the skin and internal organs. Because its aetiology is unknown, the identification of genes/factors involved in disease severity, differential clinical forms, and associated complications is critical for understanding its pathogenesis and designing novel treatments. Neuroendocrine mediators in the skin emerge as potential candidates. We investigated the role played by the neuropeptide cortistatin in a preclinical model of scleroderma. METHODS: RESULTS: An inverse correlation between cortistatin levels and fibrogenic activation exists in the damaged skin and dermal fibroblasts. Bleomycin-challenged skin lesions of mice that are partially and totally deficient in cortistatin showed exacerbated histopathological signs of scleroderma, characterized by thicker and more fibrotic dermal layer, enlarged epidermis, and increased inflammatory infiltration in comparison to those of wild-type mice. Cortistatin deficiency enhanced dermal collagen deposits, connective tissue growth factor expression, loss of microvessels, and predisposition to suffer severe complications that co-occur with dermal exposition to bleomycin, including pulmonary fibrotic disease and increased mortality. Treatment with cortistatin mitigated these pathological processes. DISCUSSION/CONCLUSION:
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Authors | Margarita Barriga, Raquel Benitez, Gema Robledo, Marta Caro, Francisco O'Valle, Jenny Campos-Salinas, Mario Delgado |
Journal | Neuroendocrinology
(Neuroendocrinology)
Vol. 112
Issue 8
Pg. 784-795
( 2022)
ISSN: 1423-0194 [Electronic] Switzerland |
PMID | 34649259
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 S. Karger AG, Basel. |
Chemical References |
- Neuropeptides
- cortistatin
- Bleomycin
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Topics |
- Animals
- Bleomycin
(toxicity)
- Disease Models, Animal
- Fibrosis
- Mice
- Neuropeptides
(metabolism)
- Pulmonary Fibrosis
(chemically induced, metabolism)
- Scleroderma, Systemic
(chemically induced, metabolism)
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