scholarly journals Nrf2/Keap1/ARE Signaling Mediated an Antioxidative Protection of Human Placental Mesenchymal Stem Cells of Fetal Origin in Alveolar Epithelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xiurui Yan ◽  
Xue Fu ◽  
Yuanyuan Jia ◽  
Xiaona Ma ◽  
Jin Tao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Caspase 3 ◽  
Antioxidative Activity ◽  
A549 Cells ◽  
Oxidative Injury ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Fetal Origin

The oxidative stresses are a major insult in pulmonary injury such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two clinical manifestations of acute respiratory failure with substantially high morbidity and mortality. Mesenchymal stem cells (MSCs) hold a promise in treatments of many human diseases, mainly owing to their capacities of immunoregulation and antioxidative activity. The strong immunoregulatory role of human placental MSCs of fetal origin (hfPMSCs) has been previously demonstrated; their antioxidant activity, however, has yet been interrogated. In this report, we examined the antioxidative activity of hfPMSCs by accessing the ability to scavenge oxidants and radicals and to protect alveolar epithelial cells from antioxidative injury using both a cell coculture model and a conditioned culture medium (CM) of hfPMSCs. Results showed a comparable antioxidative capacity of the CM with 100 μM of vitamin C (VC) in terms of the total antioxidant capacity (T-AOC), scavenging abilities of free radicals DPPH, hydroxyl radical (·OH), and superoxide anion radical (O2-), as well as activities of antioxidant enzymes of SOD and GSH-PX. Importantly, both of the CM alone and cocultures of hfPMSCs displayed a protection of A549 alveolar epithelial cells from oxidative injury of 600 μM hydrogen peroxide (H2O2) exposure, as determined in monolayer and transwell coculture models, respectively. Mechanistically, hfPMSCs and their CM could significantly reduce the apoptotic cell fraction of alveolar epithelial A549 cells exposed to H2O2, accompanied with an increased expression of antiapoptotic proteins Bcl-2, Mcl-1, Nrf-2, and HO-1 and decreased proapoptotic proteins Bax, caspase 3, and Keap1, in comparison with naïve controls. Furthermore, hfPMSCs-CM (passage 3) collected from cultures exposed an inhibition of the Nrf2/Keap1/ARE signaling pathway which led to a significant reduction in caspase 3 expression in A549 cells, although the addition of Nrf2 inhibitor ML385 had no effect on the antioxidative activity of hfPMSCs-CM. These data clearly suggested that hfPMSCs protected the H2O2-induced cell oxidative injury at least in part by regulating the Nrf2-Keap1-ARE signaling-mediated cell apoptosis. Our study thus provided a new insight into the antioxidative mechanism and novel functions of hfPMSCs as antioxidants in disease treatments, which is warranted for further investigations.

scholarly journals Origin of Myofibroblasts in Lung Fibrosis

2020 ◽  
Vol 1 (4) ◽  
pp. 155-162
Author(s):  
CF Hung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Lung Fibrosis ◽  
Cell Types ◽  
Mesenchymal Cells ◽  
Lineage Tracing ◽  
Alveolar Epithelial Cells ◽  
Multiple Sources ◽  
Alveolar Epithelial

Abstract Purpose of Review In this brief review, we will highlight important observational and experimental data in the literature that address the origin of scar-forming cells in lung fibrosis. Recent Findings Several cellular sources of activated scar-forming cells (myofibroblasts) have been postulated including alveolar epithelial cells; circulating fibrocytes; and lung stromal cell subpopulations including resident fibroblasts, pericytes, and resident mesenchymal stem cells. Recent advances in lineage-tracing models, however, fail to provide experimental evidence for epithelial and fibrocyte origins of lung myofibroblasts. Resident mesenchymal cells of the lung, which include various cell types including resident fibroblasts, pericytes, and resident mesenchymal stem cells, appear to be important sources of myofibroblasts in murine models of lung injury and fibrosis. Summary Lung myofibroblasts likely originate from multiple sources of lung-resident mesenchymal cells. Their relative contributions may vary depending on the type of injury. Although lineage-tracing experiments have failed to show significant contribution from epithelial cells or fibrocytes, they may play important functional roles in myofibroblast activation through paracrine signaling.

scholarly journals Differentiation of Bone Marrow Mesenchymal Stem Cells into Alveolar Epithelial Cells Reduces Radiation-Induced Lung Injury by Regulating Angii/ACE2/Ang(1-7) Axis and Suppressing NF-Κb/MAPK Pathway

2021 ◽  
Author(s):  
shiying niu ◽  
changsheng cong ◽  
zhaopeng wang ◽  
meili sun ◽  
yueying zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Lung Tissue ◽  
Mapk Pathway ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Qrt Pcr ◽  
Radiation Induced

Abstract Background Radiation-induced lung injury (RILI) is one of the most common complications of thoracic tumors radiotherapy. Since therapeutic strategies remains limited, the exploration of new approaches to treat RILI is on high demands. The use of bone mesenchymal stem cells (BMSCs) to treat RILI holds great promise thanks to their multidifferentiation and anti-inflammatory potential after injury. Here, we investigate the therapeutic potential of BMSCs in RILI. Methods Forty five C57BL/6 mice were randomly divided into groups. Except for the control group, all mice received chest irradiation. Within 24 hours after irradiation, BMSCs were injected into the tail vein of mice in BMSCs group. At 4 weeks after irradiation, all mice were dissected. HE staining and immunohistochemistry were used to observe the pathological changes of lung tissue and the expression of inflammatory factors. Immunofluorescence technique was used to detect whether BMSCs migrated to lung tissue and to verify their differentiation potential. The expression of Ang II and Ang (1-7) in lung tissue was detected by ELISA. The expression of MasR mRNA in lung tissue was detected by qRT-PCR. Western blotting was used to detect the expression of ACE2, ACE, AT1R and MAPK related proteins. Results we found that BMSCs significantly reduced RILI by HE and immunohistochemistry. Immunofluorescence results showed that BMSCs migrated to injuried lung tissue and differentiated into alveolar epithelial cells. Combined with qRT-PCR and Western blotting results showed BMSCs significantly up-regulated ACE2/Ang(1-7)/MasR axis and suppressed NF-κB/MAPK pathway. Conclusions The study demonstrated that BMSCs may be transplanted into damaged lung tissue where they differentiated into AEC II to regulate AngII/ACE2/Ang(1-7) axis and suppress NF-κB/MAPK pathway to alleviate RILI.

Bleomycin-induced apoptosis of alveolar epithelial cells requires angiotensin synthesis de novo

2003 ◽  
Vol 284 (3) ◽  
pp. L501-L507 ◽  
Author(s):  
Xiaopeng Li ◽  
Huiying Zhang ◽  
Valerie Soledad-Conrad ◽  
Jiaju Zhuang ◽  
Bruce D. Uhal
Keyword(s):  
Epithelial Cells ◽  
Caspase 3 ◽  
De Novo ◽  
Enzyme Inhibitor ◽  
Primary Cultures ◽  
A549 Cells ◽  
Cell Loss ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Induced Apoptosis

Primary cultures of rat type II alveolar epithelial cells (AECs) or human AEC-derived A549 cells, when exposed to bleomycin (Bleo), exhibited concentration-dependent apoptosis detected by altered nuclear morphology, fragmentation of DNA, activation of caspase-3, and net cell loss over time. In both cell culture models, exposure to Bleo caused time-dependent increases in angiotensinogen (ANGEN) mRNA. Antisense oligonucleotides against ANGEN mRNA inhibited Bleo-induced apoptosis of rat AEC or A549 cells by 83 and 84%, respectively ( P < 0.01 and P < 0.05), and prevented Bleo-induced net cell loss. Apoptosis of rat AECs or A549 cells in response to Bleo was inhibited 91% by the ANG-converting enzyme inhibitor captopril or 82%, respectively, by neutralizing antibodies specific for ANG II (both P < 0.01). Antagonists of ANG receptor AT1 (losartan, L-158809, or saralasin), but not an AT2-selective blocker (PD-123319), inhibited Bleo-induced apoptosis of either rat AECs (79%, P < 0.01) or A549 cells (83%, P < 0.01) and also reduced the activity of caspase-3 by 52% ( P < 0.05). These data indicate that Bleo, like FasL or TNF-α, induces transactivation of ANG synthesis de novo that is required for AEC apoptosis. They also support the theory that ANG system antagonists have potential for the blockade of AEC apoptosis in situ.

Mesenchymal stem cells reduce hypoxia-induced apoptosis in alveolar epithelial cells by modulating hypoxic signaling

2015 ◽  
Author(s):  
Olivier Bernard ◽  
Florence Jeny ◽  
Elisabetta Dondy ◽  
Yurdagül Uzunhan ◽  
Shalini Sivarajah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Induced Apoptosis
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