Zhou Tian-Biao, Drummen Gregor P C, Qin Yuan-Han
Department of Pediatric Nephrology, the First Affiliated Hospital of Guangxi Medical University, 1 Nanning 53002, China.
Int J Mol Sci. 2012 Dec 21;14(1):226-43. doi: 10.3390/ijms14010226.
Fibrotic diseases, such as liver, pulmonary and renal fibrosis, are common end-stage conditions and represent a major global health problem. Furthermore, effective therapeutic measures are presently unavailable. Extracellular matrix accumulation is the most prominent characteristic in the pathogenesis of fibrotic disease. Retinoic acid, including all-trans retinoic acid, 9-cis and 13-cis retinoic acid, play important roles in various physiological processes, such as in embryonic development, reproduction, vision, cell growth, differentiation, apoptosis and inflammation. Present studies report that retinoic acid treatment may affect various processes involved in the onset and progression of fibrotic disease. However, the therapeutic effects of retinoic acid in such diseases remain controversial. Several reports indicate that retinoic acid positively affects the progression of fibrosis and alleviates the accumulation of the extracellular matrix, whereas other studies report the opposite; that retinoic acid exacerbates fibrosis and induces extracellular matrix accumulation. Signaling pathways might be an important influencing factor and differences in signaling events might be responsible for the contradictory role of retinoic acid in fibrotic diseases. Since there was no review available that investigated the role of retinoic acid and the signaling pathways involved, we retrospectively studied the literature and provide a comprehensive analysis of retinoic acid's role in fibrotic diseases, and provide an overview of the signal transduction pathways involved in its pathogenesis.
纤维化疾病，如肝纤维化、肺纤维化和肾纤维化，是常见的终末期病症，也是一个重大的全球健康问题。此外，目前尚无有效的治疗措施。细胞外基质积聚是纤维化疾病发病机制中最突出的特征。维甲酸，包括全反式维甲酸、9-顺式维甲酸和13-顺式维甲酸，在各种生理过程中发挥重要作用，如胚胎发育、生殖、视觉、细胞生长、分化、凋亡和炎症。目前的研究报告称，维甲酸治疗可能会影响纤维化疾病发生和发展过程中的各种进程。然而，维甲酸在这类疾病中的治疗效果仍存在争议。一些报告表明，维甲酸对纤维化进程有积极影响，并减轻细胞外基质的积聚，而其他研究则报告了相反的结果；即维甲酸会加剧纤维化并诱导细胞外基质积聚。信号通路可能是一个重要的影响因素，信号事件的差异可能是维甲酸在纤维化疾病中作用相互矛盾的原因。由于目前尚无综述研究维甲酸的作用及相关信号通路，我们对文献进行了回顾性研究，全面分析了维甲酸在纤维化疾病中的作用，并概述了其发病机制中涉及的信号转导通路。
