Carnevali S, Mio T, Adachi Y, Spurzem J R, Striz I, Romberger D J, Illig M, Rennard S I
Clinica di Malattie Dell'Apparato Respiratorio, Dipartimento Misto di Specialità Mediche e Chirurgiche, Università degli Studi di Modena e Reggio Emilia Policlinico, 71, Modena 41100, Italy.
Tissue Cell. 2003 Dec;35(6):459-69. doi: 10.1016/s0040-8166(03)00072-7.
Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role in the production and modification of extracellular matrix in wound repair. Since one important aspect of wound repair is the contraction of the wound, this study investigated the effects of radiation on the ability of fibroblasts to mediate collagen gel contraction in an in vitro model of wound retraction. After irradiation, the cells were detached and suspended in a solution of rat tail tendon collagen. Radiation exposure decreased retraction, and this effect was dose dependent. In order to define the mechanism of reduced gel retraction, we investigated alpha2beta1 cell surface integrin and fibronectin, which are thought to mediate contraction, and prostaglandin E2 (PGE2), which is known to inhibit this process. PGE2 release increased dose responsively following radiation. The cyclooxygenase inhibitor indomethacin could partially restore the contractile activity of irradiated fibroblasts. Fibronectin production in gel culture showed a significant decrease. In contrast, there was no decrease in alpha2beta1 integrin expression in radiated cells. In conclusion, radiation decreases fibroblast-mediated gel contraction. Increased PGE2 production and decreased fibronectin production by irradiated fibroblasts may contribute to this effect and may be in part responsible for poor healing of radiated tissue.
已知辐射暴露会损害受辐射区域的愈合。成纤维细胞在伤口修复中细胞外基质的产生和修饰过程中起主要作用。由于伤口修复的一个重要方面是伤口收缩，本研究在伤口回缩的体外模型中，研究了辐射对成纤维细胞介导胶原凝胶收缩能力的影响。辐射后，细胞被分离并悬浮于大鼠尾腱胶原溶液中。辐射暴露降低了回缩，且这种效应呈剂量依赖性。为了确定凝胶回缩减少的机制，我们研究了被认为介导收缩的α2β1细胞表面整合素和纤连蛋白，以及已知会抑制这一过程的前列腺素E2（PGE2）。辐射后PGE2释放呈剂量依赖性增加。环氧化酶抑制剂吲哚美辛可部分恢复受辐射成纤维细胞的收缩活性。凝胶培养中纤连蛋白的产生显著减少。相比之下，辐射细胞中α2β1整合素的表达没有下降。总之，辐射会降低成纤维细胞介导的凝胶收缩。受辐射的成纤维细胞中PGE2产生增加和纤连蛋白产生减少可能导致了这种效应，并且可能部分导致了受辐射组织愈合不良。
