缺氧诱导因子1α与瘢痕疙瘩肿瘤特性及其放疗抵抗

Research progress of hypoxia-inducible factor 1 alpha in tumor-like characteristics of keloid and its radioresistance

背景:瘢痕疙瘩是一种创伤后成纤维细胞大量增殖和胶原过度沉积的良性皮肤肿瘤。瘢痕疙瘩组织内血管闭塞、炎症和成纤维细胞的增殖及胶原分泌等高代谢行为均导致组织乏氧,组织乏氧在瘢痕疙瘩的发病和预后中起重要作用。目的:就缺氧诱导因子1α在瘢痕疙瘩肿瘤特性中的研究进展作一综述。方法:检索知网数据库(CNKI)、维普数据库及万方数据平台,PubMed数据库、Biosos Preview数据库及Web of Science数据库从建库至2020年11月的相关文献,中英文检索词分别为"瘢痕疙瘩;缺氧诱导因子1;放疗抵抗""keloids;HIF-lα;Radioresistance"。经过阅读文题、摘要和全文的逐步筛选,最终纳入104篇符合入选标准的文献。结果与结论:乏氧微环境抑制缺氧诱导因子1α的降解,增多的缺氧诱导因子1α可诱导瘢痕疙瘩产生上皮间质转化、血管生成、糖酵解、放疗抵抗等类似于恶性肿瘤的生物学行为,而这些病理生理过程又加重组织乏氧,使得缺氧诱导因子1α呈指数增加,形成恶性循环。目前,瘢痕疙瘩的治疗仍以手术切除联合放疗为主。以缺氧诱导因子1α为靶点的治疗,如高压氧治疗治疗,可以显著改善瘢痕疙瘩组织的乏氧环境,促进伤口的愈合,逆转瘢痕疙瘩成纤维细胞的肿瘤特性,但目前关于高压氧治疗辅助手术联合放疗治疗瘢痕疙瘩的研究并不多,靶向瘢痕疙瘩缺氧诱导因子1α的临床治疗仍在探索中。

BACKGROUND: Keloid is a benign skin tumor with excessive proliferation of fibroblasts and deposition of collagen after trauma. Vascular occlusion, inflammation, fibroblast proliferation and collagen secretion in keloid tissues all lead to tissue hypoxia, which plays an important role in the pathogenesis and prognosis of keloids. OBJECTIVE: To review the research progress of hypoxia-inducible factor 1 alpha(HIF-1α) in the tumor-like characteristics of keloid.METHODS: CNKI, VIP, WanFang, PubMed, Biosos Preview, and Web of Science databases were searched for relevant articles from their inception to November 2020. The retrieval key words were "keloids, HIF-lα;radioresistance" in Chinese and English, respectively. After reading the title, abstract and full text, 104 articles that met the selection criteria were finally selected.RESULTS AND CONCLUSION: The hypoxic microenvironment inhibits the degradation of HIF-1α, and increased HIF-1α induces several biological behaviors in keloid tissue similar to malignant tumors, including epithelial-mesenchymal transition, angiogenesis, glycolysis, radioresistance, and recurrence after radiation. These pathophysiological processes in turn exacerbate tissue hypoxia and increase HIF-1αexponentially, thereby forming a vicious circle. Current treatments for keloids mainly focus on surgical resection combined with radiotherapy. HIF-1α targeting therapies, such as hyperbaric oxygen therapy, can significantly improve the hypoxic environment of keloid tissue, promote wound healing, and reverse the tumor-like properties of keloid fibroblasts. However, there are few studies on the treatment of keloids with hyperbaric oxygen therapy combined with radiotherapy, and the clinical treatment of keloids with HIF-1α as the target is still under exploration.