循环纤维细胞通过SDF-1调控瘢痕疙瘩成纤维细胞的作用及其机制研究

Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. The pathomechanisms and treatment strategies of keloids are still big problem in plastic surgery.. Circulating fibrocytes play an important role in trauma and fibrosis by adjusting the activity of fibroblasts. It has been confirmed that circulating fibrocytes are closely related to keloids. Circulating fibrocytes can secret SDF-1, which’ receptor is found in keloids. Furthermore, we found SDF-1 and supernatant of circulating fibrocytes both could augment fibroblast proliferation. In conclusion, we assume circulating fibrocytes might modulate keloids fibroblasts by SDF-1, resulting affecting fibrosis in keloids..The aim of this study is to find the functions and mechanisms of circulating fibrocytes modulating keloid fibroblasts, by co-cultivating circulating fibrocytes and fibroblasts, interfering the possible pathways, and observing the variation of indicators. The role and mechanism of circulating fibrocytes in keloids, which is not reported yet, can provide us a new understanding of keloids and treatments. Furthermore, if so, the treatment strategies about circulating fibrocytes will be quite safe and useful for no circulating fibrocytes in normal skin.

瘢痕疙瘩病理学表现为成纤维细胞增殖加速和大量细胞外基质的合成，其形成机制和治疗仍是整形外科重大难题之一。循环纤维细胞是近年创伤和纤维化研究的又一热点，它能通过调控成纤维细胞的功能来发挥作用。已有研究证实，它与瘢痕疙瘩的发生密切相关。SDF-1是循环纤维细胞分泌的趋化因子之一，瘢痕疙瘩组织中有其受体的阳性表达。预实验中发现，SDF-1和循环纤维细胞上清液都能促进瘢痕疙瘩成纤维细胞增殖。综上我们猜测，循环纤维细胞可能通过SDF-1 促进成纤维细胞的增殖和胶原合成，从而影响瘢痕疙瘩中纤维化过程。本实验拟通过循环纤维细胞与成纤维细胞共培养、干预可能的调控途径，观察相关通路和纤维化指标的变化，探讨循环纤维细胞是通过SDF-1调控瘢痕疙瘩成纤维细胞的作用和机制。目前国内外尚无相关研究报道。另外若假设成立，由于正常组织中没有循环纤维细胞，针对该细胞的治疗也无相应的靶点，有较高的安全性和很好的前景。

瘢痕疙瘩病理学表现为成纤维细胞增殖加速和大量细胞外基质的合成。循环纤维细胞能通过调控成纤维细胞的功能来影响纤维化的过程，已有研究证实，它与瘢痕疙瘩的发生密切相关。SDF-1是循环纤维细胞分泌的趋化因子之一，瘢痕疙瘩组织中有其受体的阳性表达。本课题研究了循环纤维细胞通过SDF-1对瘢痕疙瘩成纤维细胞的作用，探讨了相关作用机制，发现循环纤维细胞的上清液能促进成纤维细胞的增殖，上调其CXCR4、TGF-β1的表达，在瘢痕疙瘩成纤维细胞中加入SDF-1后，发现细胞增殖显著， CXCR4、PI3K、TGF-β1 、Col-I表达增加，而CXCR4 受体拮抗剂、PI3K 拮抗剂的加入都能抑制循环纤维细胞的上清液、SDF-1对瘢痕疙瘩成纤维细胞的相关上调作用。结果提示，循环纤维细胞可能通过SDF-1 来上调瘢痕疙瘩成纤维细胞的增殖、合成分泌胶原的功能，这可能是通过PI3K/AKT 信号通路完成的。这为探明循环纤维细胞通过SDF-1 对瘢痕疙瘩成纤维细胞的作用和机制并为治疗该疾病提供理论依据。由于在正常组织中没有循环纤维细胞，针对该细胞的治疗也无相应的靶点，所以其临床应用应该有较高的安全性，有很好的应用前景。