From the Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic Surgery, and Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine.
Plast Reconstr Surg. 2022 Aug 1;150(2):327-338. doi: 10.1097/PRS.0000000000009363. Epub 2022 Jun 6.
Striae distensae are common disfiguring cutaneous lesions but lack effective treatments because of an incomplete understanding of their pathophysiology. Dermal fibroblasts likely play an important role. The authors investigate the cellular-molecular features distinguishing fibroblasts from human striae distensae and normal skin. The authors also develop a mouse model of striae distensae.
Human striae distensae and normal skin samples were compared for tensile strength and histologic structure. Fibroblasts from striae distensae and normal skin were isolated by fluorescence-activated cell sorting for gene expression analysis. Immunofluorescence staining and fluorescence-activated cell sorting were used to confirm gene expression data at the protein level. A mouse model of striae distensae formation was created by administering corticosteroids and mechanically loading the dorsal skin.
Human striae distensae exhibited reduced tensile strength, more disordered collagen fibers, and epidermal atrophy compared to human normal skin. There were 296 up-regulated genes in striae distensae fibroblasts, including the profibrotic lineage and surface marker CD26. Up-regulated genes were involved in profibrotic and mechanoresponsive signaling pathways (TGFβ and FAK-PI3-AKT-signaling). In contrast, 571 genes were down-regulated, including CD74 and genes of the AMPK pathway. Increased CD26 and decreased CD74 expression was confirmed by fluorescence-activated cell sorting and immunofluorescence. Similar cutaneous histologic and gene expression changes were induced in hypercortisolemic mice by mechanically loading the dorsal skin.
Fibroblasts from human striae distensae exhibit increased profibrotic and decreased antifibrotic signaling. CD26 and CD74 are promising surface markers that may be targeted therapeutically. The authors' mouse model of striae distensae can be used as a platform to test the efficacy of potential therapeutic agents.
Striae distensae are common disfiguring cutaneous lesions whose etiology remains elusive, which has hindered development of effective treatment strategies. Dermal fibroblasts likely play an important role. The authors sought to elucidate the key cellular-molecular pathways distinguishing fibroblasts in striae distensae from those in normal skin.
妊娠纹是常见的皮肤损伤，但由于对其病理生理学的认识不完整，缺乏有效的治疗方法。真皮成纤维细胞可能起着重要作用。作者研究了区分人妊娠纹和正常皮肤的成纤维细胞的细胞-分子特征。作者还开发了一种妊娠纹的小鼠模型。
比较人妊娠纹和正常皮肤的拉伸强度和组织学结构。通过荧光激活细胞分选分离来自妊娠纹和正常皮肤的成纤维细胞，进行基因表达分析。免疫荧光染色和荧光激活细胞分选用于在蛋白质水平上验证基因表达数据。通过给予皮质类固醇并机械加载背部皮肤来创建妊娠纹形成的小鼠模型。
与正常皮肤相比，人妊娠纹的拉伸强度降低，胶原纤维更紊乱，表皮萎缩。妊娠纹成纤维细胞中有 296 个上调基因，包括促纤维化谱系和表面标记物 CD26。上调的基因参与促纤维化和机械反应信号通路（TGFβ和 FAK-PI3-AKT 信号通路）。相反，有 571 个基因下调，包括 CD74 和 AMPK 通路的基因。通过荧光激活细胞分选和免疫荧光证实了 CD26 的增加和 CD74 的表达减少。通过机械加载背部皮肤，在高皮质醇血症小鼠中诱导了类似的皮肤组织学和基因表达变化。
来自人妊娠纹的成纤维细胞表现出增加的促纤维化和减少的抗纤维化信号。CD26 和 CD74 是有前途的表面标记物，可能成为治疗的靶点。作者的妊娠纹小鼠模型可作为测试潜在治疗剂疗效的平台。
妊娠纹是常见的皮肤损伤，其病因仍然难以捉摸，这阻碍了有效治疗策略的发展。真皮成纤维细胞可能起着重要作用。作者试图阐明区分妊娠纹和成纤维细胞的关键细胞-分子途径与正常皮肤的成纤维细胞。
