Bone Marrow Mesenchymal Stem Cells Derived MiRNA-130b Enhances Epithelial Sodium Channel by Targeting PTEN

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2020 Dec 14

PMID 33308227

Citations 4

Authors

Honglei Zhang

Yan Ding

Yapeng Hou

Yanhong Liu

Zhiyu Zhou

Hongguang Nie

Affiliations

Soon will be listed here.

Abstract

Aims: Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality, and severe pulmonary edema is one of the characteristics. Epithelial sodium channel (ENaC) located on the apical side of alveolar type 2 epithelial (AT2) cells is the primary rate limiting segment in alveolar fluid clearance. Many preclinical studies have revealed that mesenchymal stem cells (MSCs) based therapy has great therapeutic potential for ALI, while the role of ENaC in this process is rarely known.

Methods: We studied the effects of bone marrow-derived MSCs (BMSCs) on the protein/mRNA expression and activity of ENaC in primary mouse AT2 and human H441 cells by co-culture with them, respectively. Moreover, the changes of miRNA-130b in AT2 cells were detected by qRT-PCR, and we studied the involvement of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and the downstream PI3K/AKT pathway in the miRNA-130b regulation of ENaC.

Results: Our results demonstrated that BMSCs could increase ENaC protein expression and function, as well as the expression level of miRNA-130b. The dual luciferase target gene assay verified that PTEN was one of the target genes of miR-130b, which showed adverse effects on the protein expression of α/γ-ENaC and PTEN in AT2 cells. Upregulating miR-130b and/or knocking down PTEN resulted in the increase of α/γ-ENaC protein level, and the protein expression of p-AKT/AKT was enhanced by miR-130b. Both α and γ-ENaC protein expressions were increased after AT2 cells were transfected with siPTEN, which could be reversed by the co-administration of PI3K/AKT inhibitor LY294002.

Conclusion: In summary, miRNA-130b in BMSCs can enhance ENaC at least partially by targeting PTEN and activating PI3K/AKT pathway, which may provide a promising new direction for therapeutic strategy in ALI.

Citing Articles

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Chen L, Yu T, Zhai Y, Nie H, Li X, Ding Y Int J Mol Sci. 2023; 24(12).

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PTEN: An Emerging Potential Target for Therapeutic Intervention in Respiratory Diseases.

Cai B, Yang L, Do Jung Y, Zhang Y, Liu X, Zhao P Oxid Med Cell Longev. 2022; 2022:4512503.

PMID: 35814272 PMC: 9262564. DOI: 10.1155/2022/4512503.

Small Extracellular Vesicles Containing miR-34c Derived from Bone Marrow Mesenchymal Stem Cells Regulates Epithelial Sodium Channel via Targeting MARCKS.

Hua Y, Han A, Yu T, Hou Y, Ding Y, Nie H Int J Mol Sci. 2022; 23(9).

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Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis.

Reyes-Jimenez E, Ramirez-Hernandez A, Santos-Alvarez J, Velazquez-Enriquez J, Pina-Canseco S, Baltierrez-Hoyos R Mol Cell Biochem. 2021; 476(12):4405-4419.

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