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Novel regulations of MEF2-A, MEF2-D, and CACNA1S in the functional incompetence of adipose-derived mesenchymal stem cells by induced indoxyl sulfate in chronic kidney disease

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Abstract

Indoxyl sulfate (IS) is a digestive intermediate product that is a known indicator of chronic kidney disease. Its toxicity has also been suggested to accelerate chronic kidney disease. Recently, mesenchymal stem cells (MSCs) have been confirmed as a potential treatment in kidney regeneration. To determine the universal alteration in gene expression, we combined high-throughput microarray technology and in vitro culture of adipose-derived mesenchymal stem cells at different doses of IS (20, 40, 60 mg/l). We found that indoxyl sulfate has a remarkable interconnection with stem cell and calcium/calmodulin-dependent kinase pathways. In vitro results showed that indoxyl sulfate exerts anti-proliferation and anti-migration effects on ADMSCs. In addition, IS effects lead to increase in apoptotic cells and cells arrested at the G1 phase. Moreover, MEF2-A, MEF2-D and CACNA1S expression significantly decreased after indoxyl sulfate treatment. It can be speculated that following treatment with indoxyl sulfate, the function of ADMSCs is decreased and ADMSCs’ ability to support renal tubule regeneration in chronic kidney disease patients may be lower.

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Abbreviations

ADMSCs:

Adipose-derived mesenchymal stem cells

IS:

Indoxyl sulfate

CKD:

Chronic kidney disease

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Acknowledgments

Computational analyses and data mining were performed using the system provided by the Bioinformatics Core at the National Cheng Kung University, which is supported by the National Science Council, Taiwan. We thank the National Science Council (NSC) of the Executive Yuan, Taiwan [NSC 101-2320-B-034-001; NSC 102-2325-B-400-005; NSC 101-2311-B-400-005-MY3; NSC 104-2320-B-034-003] for their support and the Grant Funding. We also thank Ministry of Science and Technology for the Grant MOST103-2325-B006-012 and 104-2917-I-006-002. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We also would like to thank Dr. Yung-Kai Lin for his technical support.

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    Authors and Affiliations

    1. Faculty of Applied Sciences, Ton Duc Thang University, Nguyen Huu Tho St., Tan Phong Ward, Dist. 7, Ho Chi Minh City, Vietnam

      Duyen Thi Do & Nam Nhut Phan

    2. Graduate Institute of Biotechnology, Chinese Culture University, 55. Hwa-Kang Rd., Yang-Ming-Shan, Taipei, 11114, Taiwan

      Duyen Thi Do & Yen-Chang Lin

    3. Department of Anatomy, University of California at San Francisco, San Francisco, CA, USA

      Chih-Yang Wang

    4. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

      Chih-Yang Wang

    5. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

      Chih-Yang Wang

    6. Department of Radiology, University of California at San Francisco, San Francisco, CA, USA

      Zhengda Sun

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    Correspondence to Yen-Chang Lin.

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    Duyen Thi Do and Nam Nhut Phan have contributed equally to this work.

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    Thi Do, D., Phan, N.N., Wang, CY. et al. Novel regulations of MEF2-A, MEF2-D, and CACNA1S in the functional incompetence of adipose-derived mesenchymal stem cells by induced indoxyl sulfate in chronic kidney disease. Cytotechnology 68, 2589–2604 (2016). https://doi.org/10.1007/s10616-016-9983-0

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