Inhibition of endotoxin-induced acute lung injury in rats by bone marrow–derived mesenchymal stem cells: Role of Nrf2/HO-1 signal axis in inhibition of NLRP3 activation

Abstract Aims: One of the characteristics of acute lung injury (ALI) is severe pulmonary edema, which is closelyrelated to alveolar fluid clearance. Mesenchymal stem cells (MSCs) secrete a wide range of cytokines,growth factors and miRNAs through paracrine action to participate in the mechanism of pulmonaryinflammatory response, which increases the clearance of edema fluid, and promotes the repair process ofALI. However, the mechanism by which bone marrow derived MSCs-conditioned medium (BMSCs-CM)promotes edema clearance is unclear. Epithelial sodium channel (ENaC) is the rate-limiting step in thesodium-water transport and edema clearance in the alveolar cavity, and we aim to explore the role of ENaCin BMSCs-CM invloved edema clearance and whether it can alter the function of ENaC via miRNAs.Methods: CCK-8 cell proliferation assay was used to detect the effect of BMSCs-CM on the survival ofAT2 cells. Real-time PCR (RT-PCR) and Western blot were used to detect the expression of ENaC in AT2cells. The effects of exosomes/miR-34c on the transepithelial short-circuit current in the monolayer of H441cells were examined by the Ussing chamber setup. Dual luciferase reporter gene assay was used to detect thetarget gene of miR-34c.Results: BMSCs-CM can increase the viability of mouse AT2 cells. RT-PCR and Western blotting resultsshowed that BMSCs-CM significantly increased the expression of γ-ENaC subunit in mouse AT2 cells.Ussing chamber assay revealed that BMSCs-CM enhanced the amiloride-sensitive currents associated withENaC activity in intact H441 cell monolayers. In addition, we observed higher expression of miR-34c inmouse AT2 cells administrated with BMSCs-CM, and the overexpression or inhibition of miR-34c canregulate the expression of ENaC protein and alter the function of ENaC. Finally, we detected MARCKS maybe one of the target gene of miR-34c.Conclusions: Our results indicate that BMSCs-CM may improve LPS-induced ALI through miR-34ctargeting MARCKS and regulating ENaC indirectly, which further explores the benefit of paracrine effectsof BMSCs on edematous ALI.

Download Full-text

Non-muscle myosin II knockdown improves survival and therapeutic effects of implanted bone marrow-derived mesenchymal stem cells in lipopolysaccharide-induced acute lung injury

Annals of Translational Medicine ◽

10.21037/atm-20-4851 ◽

2021 ◽

Vol 9 (3) ◽

pp. 262-262

Author(s):

Guosheng Wu ◽

Fei Chang ◽

He Fang ◽

Xingfeng Zheng ◽

Mingzhu Zhuang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Myosin Ii ◽

Therapeutic Effects ◽

Muscle Myosin

Download Full-text

Bone Marrow Mesenchymal Stem Cells Ameliorates Seawater-Exposure-Induced Acute Lung Injury by Inhibiting Autophagy in Lung Tissue

Pathology Research International ◽

10.1155/2014/104962 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Qiu-ping Liu ◽

Dang-xia Zhou ◽

Li Sun ◽

Luo Ling ◽

Chang-gui Wu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Blood Gas ◽

Lung Weight ◽

Arterial Blood Gas ◽

Arterial Blood ◽

Marrow Mesenchymal Stem Cells

Seawater drowning can lead to acute lung injury (ALI). Several studies have shown that bone marrow mesenchymal stem cells (BMSC) treatment could attenuate ALI. However, the mechanisms underlying this phenomenon still remain elusive. Therefore, this study aimed to investigate whether BMSC treatment can ameliorate seawater-induced ALI and its underlying mechanisms in a rat model. In this study, arterial blood gas, lung weight coefficient, and TNF-α, and IL-8 in bronchoalveolar lavage fluid (BALF), as well as histopathology examination, were used to detect the lung injury of seawater exposure. Moreover, western blot and RT-PCR were used to explore autophagy in lung tissues. The results demonstrated that seawater exposure induced ALI including impaired arterial blood gas, pulmonary edema, histopathologic changes, and inflammatory response in lung tissues. What is more, these changes were partly ameliorated by BMSC treatment through inhibition of autophagy in lung tissues. The application of BMSC may be a potential effective treatment for seawater-induced ALI.

Download Full-text