Regulation of retinoic acid synthetic enzymes by WT1 and HDAC inhibitors in 293 cells

Li,Yifan; Wang,Lei; Ai,Weipeng; He,Nianhui; Zhang,Lin; Du,Jihui; Wang,Yong; Mao,Xingjian; Ren,Junqi; Xu,Dan; Zhou,Bei; Li,Rong; Mai,Liwen

doi:10.3892/ijmm.2017.3051

Regulation of retinoic acid synthetic enzymes by WT1 and HDAC inhibitors in 293 cells

Authors:
- Yifan Li
- Lei Wang
- Weipeng Ai
- Nianhui He
- Lin Zhang
- Jihui Du
- Yong Wang
- Xingjian Mao
- Junqi Ren
- Dan Xu
- Bei Zhou
- Rong Li
- Liwen Mai
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Affiliations: Central Laboratory, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China, Department of Clinical Pharmacology, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China, Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, P.R. China, Department of Gastroenterology, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China, Department of Pathology, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China, Department of Clinical Laboratory, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China
Published online on: July 3, 2017 https://doi.org/10.3892/ijmm.2017.3051
Pages: 661-672
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

All-trans retinoic acid (atRA), which is mainly generated endogenously via two steps of oxidation from vitamin A (retinol), plays an indispensible role in the development of the kidney and many other organs. Enzymes that catalyze the oxidation of retinol to generate atRA, including aldehyde dehydrogenase 1 family (ALDH1)A1, ALDH1A2 and ALDH1A3, exhibit complex expression patterns at different stages of renal development. However, molecular triggers that control these differential expression levels are poorly understood. In this study, we provide in vitro evidence to demonstrate that Wilms' tumor 1 (WT1) negatively regulates the expression of the atRA synthetic enzymes, ALDH1A1, ALDH1A2 and ALDH1A3, in the 293 cell line, leading to significant blockage of atRA production. Furthermore, we demonstrate that the suppression of ALDH1A1 by WT1 can be markedly attenuated by histone deacetylase inhibitors (HDACis). Taken together, we provide evidence to indicate that WT1 and HDACs are strong regulators of endogenous retinoic acid synthetic enzymes in 293 cells, indicating that they may be involved in the regulation of atRA synthesis.

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