Proteomic Profiling of Fibroblasts Isolated from Chronic Wounds Identifies Disease-Relevant Signaling Pathways
Proteomic Profiling of Fibroblasts Isolated from Chronic Wounds Identifies Disease-Relevant Signaling Pathways
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DOI：
10.1016/j.jid.2020.02.040
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发表时间：
2020-11-01
影响因子：
6.5
通讯作者：
Dengjel, Joern
中科院分区：
文献类型：
--
作者：
Berberich, Bettina;Thriene, Kerstin;Dengjel, Joern
慢性皮肤伤口伴随许多流行的与年龄相关的疾病，是发病和死亡的主要原因。角质形成细胞和成纤维细胞都有助于慢性皮肤伤口的病理机制。表皮失调途径已被广泛研究，但对于真皮成纤维细胞对慢性伤口的影响知之甚少。我们从慢性伤口中分离出成纤维细胞，在体外繁殖它们，并使用蛋白质组分析结合蛋白质组变化的功能表征对其进行分析。慢性伤口相关成纤维细胞表现出独特的蛋白质组特征，其特征是溶酶体功能障碍和 TGFβ 信号传导失调。它们表现出细胞增殖和迁移倾向降低，同时收缩细胞外基质的能力增强。凭借这些特性，慢性伤口相关成纤维细胞会积极导致病理性无法闭合伤口，并成为改变细胞表型的药物干扰的潜在目标。
Chronic skin wounds accompany many prevalent age-related diseases and are a major cause of morbidity and mortality. Both keratinocytes and fibroblasts contribute to the pathomechanisms in chronic skin wounds. Dysregulated pathways in the epidermis have been extensively studied, but little is known of the influence of dermal fibroblasts on chronic wounding. We isolated fibroblasts from chronic wounds, propagated them in vitro, and analyzed them using proteomic profiling in combination with functional characterization of the proteomic changes. Chronic wound-associated fibroblasts exhibit a unique proteome profile characteristic of lysosomal dysfunction and dysregulated TGF beta signaling. They display a decreased propensity for cell proliferation and migration, combined with an enhanced ability to contract the extracellular matrix. With these properties, chronic wound-associated fibroblasts actively contribute to pathological inabilities to close wounds and represent potential targets for pharmacological interference for changing cellular phenotypes.