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Acid loading stimulates rat glomerular mesangial cells proliferation through Na+–H+ exchanger isoform 1 (NHE1)-dependent pathway

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Abstract

The role of metabolic acidosis in the progression of chronic kidney disease (CKD) remains unclear. The aim of the present study was to investigate the direct effects of acid loading on the proliferation of rat glomerular mesangial cells (GMCs) in vitro and the possible role of sodium–hydrogen ion exchanger isoform 1 (NHE1). Rat GMCs were treated with acidic medium as acid loading. Growth and proliferation of GMCs was studied by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, thymidine (3H-TdR) incorporation, and flow cytometry. NHE1 protein expression and activity were quantified by Western blot and dual wavelength epifluorescent illumination with 2′,7′-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. 5-(N,N-dimethyl) amiloride hydrochloride (DMA), a specific inhibitor of NHE1, was used to investigate the possible involvement of NHE1 in the proliferation of GMCs. The MTT assay, 3H-TdR incorporation, and cell cycle distribution analysis indicated that acid loading stimulated the proliferation of GMCs. Acid loading increased NHE1 activity, but had no effects on NHE1 expression at the protein level. The effects of acid loading on the proliferation of GMCs were inhibited by DMA. Acid loading induced GMC proliferation through NHE1-dependent pathways. Our findings may contribute to the understanding of metabolic acidosis in the progression of CKD.

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Acknowledgments

This work was supported by research grant #2012CB517700 from the Major State Basic Research Development Program of China (to YG), the third stage elaborate experimental project from Tongji University (to KL), and the National Natural Science Foundation of China (NSFC) Research Fund for International Young Scientists (81250110087 to JF).

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Authors and Affiliations

  1. Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China

    Kun Li, Chang-jie Chen & Yong-yu Li

  2. Division of Nephrology, Huashan Hospital, Fudan University, 12 Urumuqi Road, Shanghai, 200040, China

    Kun Li, Man Li, Lin-yun Lai, Ming-min Zhang, Shao-jun Liu, Ai Peng, Chuan-ming Hao, Yong Gu & Shan-yan Lin

  3. Department of Pathology, 9th People’s Hospital, Jiao Tong University, Shanghai, China

    Wei Su

  4. Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Łódź, Łódź, Poland

    Jakub Fichna

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  1. Kun Li
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  2. Wei Su
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  3. Man Li
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  4. Chang-jie Chen
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  9. Jakub Fichna
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  10. Ai Peng
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  11. Chuan-ming Hao
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  12. Yong Gu
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  13. Shan-yan Lin
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Corresponding author

Correspondence to Yong Gu.

Additional information

Kun Li and Wei Su contributed equally to this study.

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Li, K., Su, W., Li, M. et al. Acid loading stimulates rat glomerular mesangial cells proliferation through Na+–H+ exchanger isoform 1 (NHE1)-dependent pathway. Naunyn-Schmiedeberg's Arch Pharmacol 386, 563–569 (2013). https://doi.org/10.1007/s00210-013-0856-1

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  • DOI: https://doi.org/10.1007/s00210-013-0856-1

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