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Increased TMEM16A Involved in Alveolar Fluid Clearance After Lipopolysaccharide Stimulation

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Abstract

Transmembrane protein 16A (TMEM16A) regulates a wide variety of cellular activities, including epithelial fluid secretion and maintenance of ion homeostasis. Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, is one of the major causes of acute lung injury (ALI). In this study, we investigated the effects of LPS on the expression of TMEM16A in LA795 cells and mouse lung tissue and the potential mechanism. Result: We detected the expression of TMEM16A in LA795 cells and mouse lung tissue by RT-PCR, Western blot, and RNA interference techniques. TMEM16A expression was significantly increased by LPS stimulation in LA795 cells and in mouse lung tissue. Moreover, the LPS-induced TMEM16A expression enhancement in lung tissue was much more prominent in the alveolar epithelial region than in bigger airway epithelial cells. The typical TMEM16A current was recorded, and LPS treatment significantly enhances the current amplitude in LA795 cells. TMEM16A shRNA or TMEM16A inhibitor (T16Ainh-A01) did not affect alveolar fluid clearance (AFC), while co-application of T16Ainh-A01 induced a stronger AFC inhibition than LPS alone. LPS notably and synchronously enhanced Akt phosphorylation (p-Akt) and TMEM16A expression in a time-dependent manner in LA795 cells. Taken together, our results suggest that TMEM16A maybe plays an important role in pathological conditions of LPS-induced ALI as a protective protein.

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Abbreviations

TMEM16A:

Transmembrane protein 16A

LPS:

Lipopolysaccharide

ALI:

Acute lung injury

AFC:

Alveolar fluid clearance

p-Akt:

Akt phosphorylation

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Acknowledgments

We thank technicians Bin Li M.D. Ph.D. and Ping Xue M.D. for their technical assistance and Prof. Yi Zhang M.D. Ph.D. and Prof. Hailin Zhang M.D. Ph.D. for providing valuable suggestions.

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Authors and Affiliations

  1. Department of Respirology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, China

    Honglin Li, Xixin Yan, Zhigang Cai, Xia Li & Huiran Zhang

  2. Department of Centralab, The Second Hospital of Hebei Medical University, Shijiazhuang, China

    Rongqin Li

  3. Department of Respirology, Hebei General Hospital, Shijiazhuang, China

    Aili Zhang

  4. Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China

    Zhiyun Niu

  5. Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China

    Weisong Duan

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  1. Honglin Li
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Correspondence to Xixin Yan.

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The use of wild-type C57BL/6 mice was approved by the Animal Care and Ethics Committee of Hebei Medical University.

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The authors declare that they have no conflicts of interest.

Grants

This work was supported by the National Nature Science Foundation of China (grant no. 81170063) and the Nature Science Foundation of Hebei Province, China (grant no H2012206110).

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Li, H., Yan, X., Li, R. et al. Increased TMEM16A Involved in Alveolar Fluid Clearance After Lipopolysaccharide Stimulation. Inflammation 39, 881–890 (2016). https://doi.org/10.1007/s10753-016-0320-8

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  • DOI: https://doi.org/10.1007/s10753-016-0320-8

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