Functional Dissection of CD26 and Its Pharmacological Inhibition by Sitagliptin During Skin Wound Healing.
Functional Dissection of CD26 and Its Pharmacological Inhibition by Sitagliptin During Skin Wound Healing.
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CD26的功能解析及其在皮肤伤口愈合过程中西格列汀的药理抑制作用
DOI：
10.12659/msm.928933
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发表时间：
2021-03-18
期刊：
影响因子：
--
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Jiang Y;Yao Y;Li J;Wang Y;Cheng J;Zhu Y
皮肤成纤维细胞是伤口愈合的主要介导因素，也是瘢痕预防和治疗的靶点。CD26是区分成纤维细胞亚群的分子标志物，在调节皮肤成纤维细胞的生物学行为以及影响皮肤伤口修复方面发挥重要作用。对特定成纤维细胞亚群进行治疗性靶向干预有望更有效地减少皮肤瘢痕形成。
通过手术在小鼠身上建立了皮肤烧伤和切除伤口愈合模型。采用免疫组织化学染色、实时逆转录聚合酶链反应（RT - PCR）和蛋白质印迹分析等方法确定伤口愈合过程中CD26的表达模式。从完整皮肤中分离出正常成纤维细胞（NFs），从伤口中分离出成纤维细胞（WFs），并通过荧光激活细胞分选技术（FACS）将它们分为4个亚组——CD26⁺ NFs、CD26⁻ NFs、CD26⁺ WFs和CD26⁻ WFs，以比较它们的增殖、迁移和胶原蛋白合成能力。进一步在体外和体内评估了西他列汀对皮肤成纤维细胞以及伤口愈合过程中CD26的药理抑制作用。
在两种模型的皮肤伤口愈合过程中均观察到CD26表达增加。从伤口中分离出的CD26⁺成纤维细胞比其他成纤维细胞亚群具有明显更强的增殖、迁移和合成胶原蛋白的能力。西他列汀治疗可显著降低CD26表达，抑制体外成纤维细胞的增殖、迁移和胶原蛋白合成，并减少体内瘢痕形成。
我们的数据表明，CD26通过调节成纤维细胞的细胞增殖、迁移和胶原蛋白合成在皮肤伤口愈合中发挥功能作用。西他列汀对CD26的药理抑制可能是一种减少皮肤瘢痕形成的可行策略。
Background Skin fibroblasts are primary mediators underlying wound healing and therapeutic targets in scar prevention and treatment. CD26 is a molecular marker to distinguish fibroblast subpopulations and plays an important role in modulating the biological behaviors of dermal fibroblasts and influencing skin wound repair. Therapeutic targeting of specific fibroblast subsets is expected to reduce skin scar formation more efficiently. Material/Methods Skin burn and excisional wound healing models were surgically established in mice. The expression patterns of CD26 during wound healing were determined by immunohistochemical staining, real-time RT-PCR, and western blot assays. Normal fibroblasts from intact skin (NFs) and fibroblasts in wounds (WFs) were isolated and sorted by fluorescence-activated cell sorting (FACS) into 4 subgroups – CD26+ NFs, CD26− NFs, CD26+ WFs, and CD26− WFs – for comparisons of their capacities of proliferation, migration, and collagen synthesis. Pharmacological inhibition of CD26 by sitagliptin in skin fibroblasts and during wound healing were further assessed both in vitro and in vivo. Results Increased CD26 expression was observed during skin wound healing in both models. The CD26+ fibroblasts isolated from wounds had significantly stronger abilities to proliferate, migrate, and synthesize collagen than other fibroblast subsets. Sitagliptin treatment potently diminished CD26 expression, impaired the proliferation, migration, and collagen synthesis of fibroblasts in vitro, and diminished scar formation in vivo. Conclusions Our data reveal that CD26 is functionally involved in skin wound healing by regulating cell proliferation, migration, and collagen synthesis in fibroblasts. Pharmacological inhibition of CD26 by sitagliptin might be a viable strategy to reduce skin scar formation.