title: Increased TMEM16A Involved in Alveolar Fluid Clearance After Lipopolysaccharide Stimulation.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Respirology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respirology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, China. yanxixin621108@sina.com.
authors.forename: Xixin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Centralab, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Rongqin
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Respirology, Hebei General Hospital, Shijiazhuang, China.
authors.forename: Aili
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Respirology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Weisong
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Respirology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respirology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Huiran
authors.initials: H
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D000075369:Anoctamin-1; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology*; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; D008070:Lipopolysaccharides; D011743:Pyrimidines; D034741:RNA, Small Interfering; C578466:T16AInh-A01; D013844:Thiazoles; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: TMEM16A; acute lung injury; alveolar fluid clearance; lipopolysaccharide; p-Akt