MicroRNA 16 modulates epithelial sodium channel in human alveolar epithelial cells.

Abstract

Acute lung injury (ALI) is a devastating disease characterized by pulmonary edema. Removal of edema from the air spaces of lung is a critical function of the epithelial sodium channel (ENaC) in ALI. The molecular mechanisms behind resolution of pulmonary edema are incompletely understood. MicroRNA's (miRNA) are crucial gene regulators and are dysregulated in various diseases including ALI. Recent studies suggest that microRNA-16 (miR-16) targets serotonin transporter (SERT) involved in the serotonin (5-HT) transmitter system. Alterations in serotonin levels have been reported in various pulmonary diseases. However, the role of miR-16 on its target SERT, and ENaC, a key ion channel involved in the resolution of pulmonary edema, have not been studied. In the present study, the expression patterns of miR-16, SERT, ENaC and serotonin were investigated in mice exposed to room air and hyperoxia. The effects of miR-16 overexpression on ENaC, SERT, TGF-β and Nedd4 in human alveolar epithelial cells were analyzed. miR-16 and ENaC were downregulated in mice exposed to hyperoxia. miR-16 downregulation in mouse lung was correlated with an increase in SERT expression and pulmonary edema. Overexpression of miR-16 in human alveolar epithelial cells (A549) suppressed SERT and increased ENaCβ levels when compared to control-vector transfected cells. In addition, miR-16 over expression suppressed TGFβ release, a critical inhibitor of ENaC. Interestingly Nedd4, a negative regulator of ENaC remained unaltered in miR-16 over expressed A549 cells when compared to controls. Taken together, our data suggests that miR-16 upregulates ENaC, a major sodium channel involved in resolution of pulmonary edema in ALI.

• Authors: Prasanna Tamarapu Parthasarathy, Lakshmi Galam, Bao Huynh, Asfiya Yunus, Toaa Abuelenen, Annie Castillo, Gurukumar Kollongod Ramanathan, Ruan Cox Jr, Narasaiah Kolliputi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 426 Issue 2 Pg. 203-8 (Sep 21 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22940131 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Endosomal Sorting Complexes Required for Transport
• Epithelial Sodium Channels
• MIRN16 microRNA, human
• MicroRNAs
• SCNN1B protein, human
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Transforming Growth Factor alpha
• Serotonin
• Nedd4 Ubiquitin Protein Ligases
• Nedd4 protein, human
• Nedd4l protein, mouse
• Ubiquitin-Protein Ligases

Topics

• Acute Lung Injury (metabolism)
• Aerobiosis
• Animals
• Cell Line, Tumor
• Endosomal Sorting Complexes Required for Transport (metabolism)
• Epithelial Sodium Channels (genetics, metabolism)
• Humans
• Mice
• MicroRNAs (genetics, metabolism)
• Nedd4 Ubiquitin Protein Ligases
• Pulmonary Alveoli (metabolism)
• Respiratory Mucosa (metabolism)
• Serotonin (metabolism)
• Serotonin Plasma Membrane Transport Proteins (genetics, metabolism)
• Transforming Growth Factor alpha (metabolism)
• Ubiquitin-Protein Ligases (metabolism)