title: Insulin up-regulates epithelial sodium channel in LPS-induced acute lung injury model in rats by SGK1 activation.
abstract: Activity of the epithelial sodium channels (ENaCs) in the lung tissue plays a critical role on sodium/fluid homeostasis and the lung fluid clearance. The serum- and glucocorticoid-inducible kinase-1 (SGK1), one of the critical regulation proteins of ENaC, is activated by insulin and growth factors possibly through 3-phosphoinositide-dependent kinase PDK1 or/and phosphatidylinositol 3-kinase (PI3K). However, it is uncertain whether insulin shows its stimulatory action on ENaC by activation of SGK1 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) condition. In our study, Wistar rats were injected with LPS to induce ALI. Evans blue dye albumin (EBA) concentration was used to measure pulmonary oedema. For detecting the ratio of phospho-SGK1/SGK1 and α-ENaC protein, Western blot was performed. Real-time polymerase chain reaction (RT-PCR) was used to assess α-ENaC messenger RNA (mRNA). Immunohistochemistry was used to locate and quantitate α-ENaC expression. The EBA concentration was markedly increased by LPS alone but significantly reduced in rats that also received insulin injection. The ratio of phospho-SGK1/SGK1 was raised significantly in the insulin group and insulin+LPS group, compared with the control group and the LPS group, respectively. Furthermore, α-ENaC was up-regulated by insulin treatment. Simultaneously, injection with LPS significantly reduced α-ENaC expression. These findings demonstrated that insulin up-regulates ENaC in vivo possibly resulting from activation of SGK1.
authors.affiliation: Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. zhutao063020@sina.com
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dao-xin
authors.initials: DX
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D001786:Blood Glucose; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D007328:Insulin; D008070:Lipopolysaccharides; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099184:Serum-Glucocorticoid Regulated Kinases