Fibrin is an essential constituent of the coagulation cascade, and the formation of hemostatic fibrin clots is central to wound healing. Fibrin clots are over time degraded into fibrin degradation products as the injured tissue is replaced by granulation tissue. Our goal was to study the role of the fibrin degradation product fragment E (FnE) in fibroblast activation and migration. We present evidence that FnE is a chemoattractant for fibroblasts and that FnE can potentiate TGF-β-induced myofibroblast formation. FnE forms a stable complex with αVβ3 integrin, and the integrin β3 subunit is required both for FnE-induced fibroblast migration and for potentiation of TGF-β-induced myofibroblast formation. Finally, subcutaneous infusion of FnE in mice results in a fibrotic response in the hypodermis. These results support a model where FnE released from clots in wounded tissue promote wound healing and fibrosis by both recruitment and activation of fibroblasts. Fibrin fragment E could thus represent a therapeutic target for treatment of pathological fibrosis.

中文翻译：

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纤维蛋白片段 E 增强 TGF-β 诱导的肌成纤维细胞活化和募集。

纤维蛋白是凝血级联的重要组成部分，止血纤维蛋白凝块的形成对伤口愈合至关重要。随着受伤组织被肉芽组织取代，纤维蛋白凝块随着时间的推移降解为纤维蛋白降解产物。我们的目标是研究纤维蛋白降解产物片段 E (FnE) 在成纤维细胞活化和迁移中的作用。我们提供的证据表明 FnE 是成纤维细胞的化学引诱剂，并且 FnE 可以增强 TGF-β 诱导的肌成纤维细胞形成。FnE 与 αVβ3 整联蛋白形成稳定的复合物，FnE 诱导的成纤维细胞迁移和增强 TGF-β 诱导的肌成纤维细胞形成都需要整联蛋白 β3 亚基。最后，在小鼠中皮下输注 FnE 会导致皮下组织发生纤维化反应。这些结果支持一个模型，其中从受伤组织中的凝块释放的 FnE 通过募集和激活成纤维细胞促进伤口愈合和纤维化。因此，纤维蛋白片段 E 可以代表治疗病理性纤维化的治疗靶点。