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Down-Regulation of ClC-3 Expression Reduces Epidermal Stem Cell Migration by Inhibiting Volume-Activated Chloride Currents

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Abstract

ClC-3, a member of the ClC chloride (Cl−) channel family, has recently been proposed as the primary Cl− channel involved in cell volume regulation. Changes in cell volume influence excitability, contraction, migration, pathogen-host interactions, cell proliferation, and cell death processes. In this study, expression and function of ClC-3 channels were investigated during epidermal stem cell (ESC) migration. We observed differential expression of CLC-3 regulates migration of ESCs. Further, whole-cell patch-clamp recordings and image analysis demonstrated ClC-3 expression affected volume-activated Cl− current (I Cl,Vol) within ESCs. Live cell imaging systems, designed to observe cellular responses to overexpression and suppression of ClC-3 in real time, indicated ClC-3 may regulate ESC migratory dynamics. We employed IMARIS software to analyze the velocity and distance of ESC migration in vitro to demonstrate the function of ClC-3 channel in ESCs. As our data suggest volume-activated Cl− channels play a vital role in migration of ESCs, which contribute to skin repair by migrating from neighboring unwounded epidermis infundibulum, hair follicle or sebaceous glands, ClC-3 may represent a new and valuable target for stem cell therapies.

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Acknowledgments

We thank our colleagues for critical advices in the preparation of this manuscript. The research was supported by Grants from the National Natural Science Foundation of China (No. 81272121).

Author Contributions

Shirong Li, Chuan Cao, and Hongli Li conceived and designed the experiments; Rui Guo, Fuqiang Pan, Yanping Tian, and Hongli Li performed the experiments; Rui Guo and Chuan Cao analyzed the data; Rui Guo and Chuan Cao wrote the manuscript.

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Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing, 400038, China

    Rui Guo, Fuqiang Pan, Shirong Li & Chuan Cao

  2. Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, China

    Yanping Tian & Hongli Li

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  1. Rui Guo
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  2. Fuqiang Pan
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  4. Hongli Li
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Correspondence to Shirong Li or Chuan Cao.

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Guo, R., Pan, F., Tian, Y. et al. Down-Regulation of ClC-3 Expression Reduces Epidermal Stem Cell Migration by Inhibiting Volume-Activated Chloride Currents. J Membrane Biol 249, 281–292 (2016). https://doi.org/10.1007/s00232-015-9867-9

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