ULTRAVIOLET-A IRRADIATION STIMULATES COLLAGENASE PRODUCTION IN CULTURED HUMAN FIBROBLASTS
ULTRAVIOLET-A IRRADIATION STIMULATES COLLAGENASE PRODUCTION IN CULTURED HUMAN FIBROBLASTS
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DOI：
10.1111/1523-1747.ep12616142
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发表时间：
1992-10-01
影响因子：
6.5
通讯作者：
CRAIG, S
中科院分区：
文献类型：
--
作者：
PETERSEN, MJ;HANSEN, C;CRAIG, S
本研究旨在探讨光化损伤皮肤中结缔组织变化的生化机制，其组织学特征为胶原纤维的减少和超微结构改变以及乳头状丹尼斯中弹性组织变性物质的沉积。我们假设紫外线可以刺激皮肤间质胶原酶的合成，导致胶原降解。用紫外线A（UVA）或紫外线B（UVB）照射单层培养的人成纤维细胞或角质形成细胞，并在照射后24 h用Western免疫印迹法在条件培养基中评估间质胶原酶或其抑制剂TIMP（金属蛋白酶组织抑制剂）。还用代表胶原酶的cDNA探针对辐射的成纤维细胞进行了北方印迹分析。在研究的所有剂量的UV辐射下，细胞活力> 90%。在0 - 10 J/cm ~ 2 UVA照射的成纤维细胞培养液中检测到免疫反应性胶原酶的剂量相关性增加，以及照射细胞中胶原酶mRNA的平行增加。UVA辐射刺激新生儿和成人成纤维细胞的胶原酶合成。UVA照射的成纤维细胞中TIMP的产生比胶原酶增加的程度要小，并且其增加与胶原酶的增加不平行。UVB（0 - 100 mJ/cm 2）不刺激成纤维细胞产生胶原酶。与成纤维细胞刺激胶原酶产生相反，UVA照射的角质形成细胞中免疫反应性胶原酶略有减少。这些数据表明，UVA辐射直接刺激人皮肤成纤维细胞胶原酶合成可能有助于紫外线辐射诱导的结缔组织损伤，导致光老化。
This study was designed to investigate the biochemical mechanisms responsible for the connective tissue changes seen in actinically damaged skin, which is characterized histologically by diminution and ultrastructural alterations of collagen fibrils and deposition of elastotic material in the papillary dennis. We hypothesized that ultraviolet light could stimulate synthesis of interstitial collagenase in the skin, resulting in collagen degradation. Monolayer cultures of human fibroblasts or keratinocytes were irradiated with ultraviolet A (UVA) or ultraviolet B (UVB) radiation and interstitial collagenase or its inhibitor, TIMP (tissue inhibitor of metalloproteinases) assessed in the conditioned medium with Western immunoblots 24 h after irradiation. Northern blot analysis of the irradiated fibroblasts with a cDNA probe representing collagenase was also performed. Cell viability was > 90% with all doses of UV radiation studied. A dose-related increase in immunoreactive collagenase was detected in the medium of fibroblasts irradiated with 0 - 10 J/cm2 of UVA radiation as well as a parallel increase in the collagenase mRNA in th irradiated cell. UVA radiation stimulated collagenase synthesis in both neonatal and adult fibroblasts. TIMP production in UVA-irradiated fibroblasts increased to a lesser degree than did collagenase and its increase did not parallel the increase in collagenase. UVB (0 - 100 mJ/cm2) did not stimulate collagenase production by fibroblasts. In contrast to the stimulation of collagenase production by fibroblasts, a slight decrease in immunoreactive collagenase was seen in UVA-irradiated keratinocytes. These data suggest that direct stimulation of collagenase synthesis by human skin fibroblasts by UVA radiation may contribute to the connective tissue damage induced by ultraviolet radiation leading to photoaging.