Parsons Amy C, Yosipovitch Gil, Sheehan Daniel J, Sangüeza Omar P, Greenberg Charles S, Sane David C
Department of Pathology, Wake Forest University Baptist Medical Center, Winston Salem, NC 27157-1045, USA.
Am J Dermatopathol. 2007 Oct;29(5):433-6. doi: 10.1097/DAD.0b013e318156e43f.
Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), occurs in renal failure patients after gadolinium contrast exposure. The fibrosis of the dermis and subcutaneous septae accompanies fibrosis of other organs, including the heart, liver, lungs, and muscle. The fibrotic skin demonstrates increased dermal collagen, fibroblasts, and mucin. The mechanism by which gadolinium is associated with fibrosis is not known. We tested the hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in the organs, including skin, of renal failure patients exposed to gadolinium contrast. We performed immunohistochemical studies using antibodies to transglutaminase-2, factor XIIIa, transglutaminase isopeptide, and the histiocyte marker CD68 on five archived skin biopsies of NSF. The results indicate that the dermal fibroblasts and histiocytes of NSF express transglutaminase-2, CD68, factor XIIIa, and transglutaminase isopeptide, indicating increased expression and/or activation of transglutaminases in NSF. We recommend further research into the use of transglutaminase inhibitors in the treatment and prevention of NSF.
肾源性系统性纤维化（NSF），也称为肾源性纤维性皮肤病（NFD），发生于接触钆对比剂后的肾衰竭患者。真皮和皮下间隔的纤维化伴有包括心脏、肝脏、肺和肌肉在内的其他器官的纤维化。纤维化皮肤表现为真皮胶原蛋白、成纤维细胞和黏蛋白增加。钆与纤维化相关的机制尚不清楚。我们检验了这样一个假说：转谷氨酰胺酶的上调促成了接触钆对比剂的肾衰竭患者包括皮肤在内的器官中所见的纤维化。我们使用针对转谷氨酰胺酶-2、因子XIIIa、转谷氨酰胺酶异肽和组织细胞标志物CD68的抗体，对5份NSF存档皮肤活检标本进行了免疫组织化学研究。结果表明，NSF的真皮成纤维细胞和组织细胞表达转谷氨酰胺酶-2、CD68、因子XIIIa和转谷氨酰胺酶异肽，表明NSF中转谷氨酰胺酶的表达和/或激活增加。我们建议进一步研究转谷氨酰胺酶抑制剂在NSF治疗和预防中的应用。
