Genetic and Molecular Drivers of Scleroderma Pathogenesis.

IF 2.3 4区 医学 Q2 DERMATOLOGY Clinics in dermatology Pub Date : 2024-12-13 DOI:10.1016/j.clindermatol.2024.12.007
Ian D Odell
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引用次数: 0

Abstract

Scleroderma is a heterogeneous disease with various clinical findings involving immune dysregulation, vasculopathy, and fibrosis. Biologic and genetic studies over recent decades have elucidated molecular mechanisms of scleroderma pathogenesis. Genetic association studies have identified interferon and other immune regulatory genes as strongly linked to scleroderma risk, highlighting the immune system as a fundamental determinant of disease. Human and murine biologic studies have identified growth factor signaling as a central feature linking tissue damage to the clinical phenotype. Growth factors activated in vascular endothelial cells overlap with those of other diseases having vascular abnormalities, such as hereditary hemorrhagic telangiectasia. Activated growth factor receptors in fibroblasts drive excessive collagen expression in the skin and lungs. Because growth factor signaling is overactivated in multiple malignancies, biologic insights and therapeutic approaches may be translated from oncology to understand scleroderma better. Enhanced understanding of the molecular drivers of scleroderma pathogenesis has given greater insight into patient phenotypes and new therapeutic approaches, including those that target immune and growth factor signaling.

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硬皮病是一种异质性疾病,临床表现多种多样,涉及免疫调节失调、血管病变和纤维化。近几十年来的生物学和遗传学研究已经阐明了硬皮病发病的分子机制。遗传关联研究发现,干扰素和其他免疫调节基因与硬皮病的发病风险密切相关,凸显了免疫系统是决定疾病的根本因素。人类和小鼠生物研究发现,生长因子信号传导是将组织损伤与临床表型联系起来的核心特征。血管内皮细胞中激活的生长因子与其他血管异常疾病(如遗传性出血性毛细血管扩张症)的生长因子重叠。成纤维细胞中被激活的生长因子受体会导致皮肤和肺部胶原蛋白过度表达。由于生长因子信号在多种恶性肿瘤中被过度激活,因此从肿瘤学中获得的生物学知识和治疗方法可以更好地理解硬皮病。对硬皮病发病机理的分子驱动因素的进一步了解使人们对患者表型和新的治疗方法(包括针对免疫和生长因子信号转导的治疗方法)有了更深入的认识。
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来源期刊
Clinics in dermatology
Clinics in dermatology 医学-皮肤病学
CiteScore
4.60
自引率
7.40%
发文量
106
审稿时长
3 days
期刊介绍: Clinics in Dermatology brings you the most practical and comprehensive information on the treatment and care of skin disorders. Each issue features a Guest Editor and is devoted to a single timely topic relating to clinical dermatology. Clinics in Dermatology provides information that is... • Clinically oriented -- from evaluation to treatment, Clinics in Dermatology covers what is most relevant to you in your practice. • Authoritative -- world-renowned experts in the field assure the high-quality and currency of each issue by reporting on their areas of expertise. • Well-illustrated -- each issue is complete with photos, drawings and diagrams to illustrate points and demonstrate techniques.
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