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The Controversial Role of Retinoic Acid in Fibrotic Diseases: Analysis of Involved Signaling Pathways
Department of Pediatric Nephrology, the First Affiliated Hospital of Guangxi Medical University, 1 Nanning 53002, China
Cellular Stress and Ageing Program, Bionanoscience and Bio-Imaging Program, Bio & Nano-Solutions, Helmutstr. 3A, Düsseldorf 40472, Germany
* Author to whom correspondence should be addressed.
Received: 1 August 2012; in revised form: 3 September 2012 / Accepted: 10 December 2012 / Published: 21 December 2012
Abstract: 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.
Keywords: fibrotic disease; fibrosis; retinoic acid; extracellular matrix; signaling pathways
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Zhou, T.-B.; Drummen, G.P.C.; Qin, Y.-H. The Controversial Role of Retinoic Acid in Fibrotic Diseases: Analysis of Involved Signaling Pathways. Int. J. Mol. Sci. 2013, 14, 226-243.
Zhou T-B, Drummen GPC, Qin Y-H. The Controversial Role of Retinoic Acid in Fibrotic Diseases: Analysis of Involved Signaling Pathways. International Journal of Molecular Sciences. 2013; 14(1):226-243.
Zhou, Tian-Biao; Drummen, Gregor P.C.; Qin, Yuan-Han. 2013. "The Controversial Role of Retinoic Acid in Fibrotic Diseases: Analysis of Involved Signaling Pathways." Int. J. Mol. Sci. 14, no. 1: 226-243.