Jianxun Lei, PhD

Mentor:  David H. Ingbar, MD

Research Project:  "Cellular and Molecular Mechanism Underlying the Regulation of Sodium Transporters in Alveolar Epithelium "

Education:     1980 – 1984, B.Sc., Huazhong
                             Agricultural University, Wuhan, China
                       1984 – 1987, M.Sc., Huazhong
                             Agricultural University, Wuhan, China
                       1991 – 1996, Ph.D., Huazhong
                             Agricultural University, Wuhan, China
                       2002 – 2007, Research Associate,
                             University of Minnesota
                       2007 – Present, Postdoctoral Trainee,
                             University of Minnesota

Project:  The trainee embarked on a new project assessing the role of the alpha7 nAChR in regulation of Na,K-ATPase (sodium pump), one of the key sodium transporters regulating alveolar fluid resorption. Thus far he has found that:  (1). The MP48 adult rat alveolar epithelial cell line, expresses alpha7 nAChR protein on western blot.; (2). Pretreatment with nicotine, an agonist of alpha7 nAChR, protected against the decrease in sodium pump activity induced by lipopolysaccharide (LPS); and (3). Hyperoxic exposure for 48 hours dramatically decreased sodium pump activity to ~40% compared with control.  Recovery for 24 hours in the presence of nicotine restored sodium pump activity to ~75% of control, whereas, sodium pump activity was restored to ~50% of control in the absence of nicotine.  Moreover, the specific antagonist of alpha7 nAChR methyllycaconitine (MLA) blocked the restorative effect of nicotine on the sodium pump activity. These data indicate that in MP48 cells nicotine restores sodium pump activity after LPS or hyperoxic injury, acting through this receptor

Specific Aims: 

Impaired alveolar fluid clearance is mainly determined by active sodium transport and decreased clearance is associated with worse respiratory failure and higher mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Active sodium transport across the alveolar epithelium is controlled by the apical amiloride-sensitive and -insensitive epithelial channels (ENaCs) and by basolateral Na,K-ATPase. Increasing the ability of alveolar epithelium to absorb the alveolar sodium should decrease mortality of patients with ALI/ARDS.

Special Aims:

• Identify signaling transduction pathways that control the upregulation of alveolar sodium transporters, particularly the sodium pump, NA,K-ATPase.
  
• Identify the protein trafficking machinery and mechanisms involved in stimulation of sodium transporters.
  
• Characterize the relationship between the signaling transduction pathways and components of protein trafficking machinery with regard to regulation of the sodium transporters.
  

Publications:

Lei J, Wangensteen OD, Ingbar DH. Activation of alpha7 nAChR restores sodium pump activity in a rat adult alveolar epithelial cell line. (Abstract 2008 American Thoracic Society International Conference May 16-21, 2008, Toronto)

Lei J, Mariash CN,  Bhargava M, Wattenberg EV, Ingbar DH.  T3 increases Na,K-ATPase activity via MAPK/ERK1/2-dependent pathway in rat adult alveolar epithelial cells. (Revision submitted to Am J Physiol (Lung)