Treatment of Hyperoxia-Induced Lung Injury with Lung Mesenchymal Stem Cells in Mice

Mei, Yabo; Chen, Chong; Dong, Hui; Zhang, Wanqiao; Wang, Yan; Ming, Chi; Feng, Zhichun

doi:10.1155/2018/5976519

Cited by 17 publications

(17 citation statements)

References 30 publications

(49 reference statements)

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“…The results showed that KIT was closely associated with VEGF-A, and known disease-related genes in BPD tissues (Figure 1C). Based on the STRING database, it was demonstrated that VEGF-A was a downstream target gene of KIT (Figure 1D) [17] and VEGF expression was down regulated in BPD as well as key genes associated with repair in BPD [18][19][20][21].…”

Section: Resultsmentioning

confidence: 99%

The Effects of Tyrosine-Protein Kinase Kit on Bronchopulmonary Dysplasia

Shi

2020

GJPNC

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Bronchopulmonary dysplasia (BPD) is a multifactorial chronic pulmonary disorder which complicates multiple pulmonary hypertensions in preterm infants. At present, there are no effective prevention or treatment options for BPD in clinical practice. Tyrosine-Protein Kinase Kit (KIT) serves an important role in regulating cell proliferation, hematopoiesis and stem cell maintenance. In the present study, the protective role of overexpression of KIT in BPD was investigated. The candidate differentially expressed genes (DEGs) between patients with BPD and healthy controls were screened using bioinformatics. A neonatal BPD mouse model was established under a hyperoxic environment and KIT overexpressing cells were intravenously injected into the mice, followed by evaluation of the effects on respiratory system resistance, pulmonary development and remodeling. Bioinformatics analysis showed that KIT was down regulated in patients with BPD, and a protein-protein interaction network was created using the Search Tool for Recurring Instances of Neighboring Genes database, which indicated that KIT was associated with known diseaserelated genes and regulated VEGF expression. In neonatal BPD mice, KIT exhibits significant protective affects and may thus serve as a candidate therapeutic target for treatment of patients with BPD treatment.

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Section: Resultsmentioning

confidence: 99%

The Effects of Tyrosine-Protein Kinase Kit on Bronchopulmonary Dysplasia

Shi

2020

GJPNC

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“…They are derived from the bone marrow, placental chorionic membrane and the lung respectively. Previous studies have shown that BMSCs, LRMSCs and hCMSCs play protective roles in lung injury caused by mechanical ventilation injury, endotoxin and plateau factors [6,8]. Other studies have reported that BMSCs can improve the lung injury caused by phosgene [4].…”

Section: Discussionmentioning

confidence: 99%

“…LRMSCs are reported to treat hyperoxia-induced lung injury in mice [6]. Studies have also con rmed that…”

Section: Introductionmentioning

confidence: 91%

Comparison of the effects of different mesenchymal stem cells on attenuating phosgene-induced lung injury in rats

Zhou

et al. 2020

Preprint

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Background Phosgene-induced lung injury is an important type of acute lung injury (ALI), which mainly leads to acute pulmonary edema. Currently, no effective clinical treatment has been developed yet. In the present study, the effects of lung-resident mesenchymal stem cells (LRMSCs), bone marrow mesenchymal stem cells (BMSCs) and human chorionic villi-derived MSCs (hCMSCs) were compared in phosgene-induced lung injury of male SD rats. Methods The changes in body weight, PaO2 and respiratory indexes were recorded. Rats were sacrificed at 6 h, 24 h, and 48 h. Expressions of TNF-α, IL-1β, IL-6, HGF and IL-10 were tested by ELISA. SP-C mRNA expression was assessed by RT-PCR. The MSCs migration was assessed using Transwell migration assay and Wound-healing assay. Hepatocyte growth factor (HGF) was added to the MSCs culture medium for 48 h. Expressions of p-GSK-3β and β-catenin were determined by Western blot. Results Significant improvements in body weight, PaO2 and respiratory indexes were observed after treatment with MSCs. BMSCs produced the highest effects followed by hCMSCs and LRMSCs. Compared with the phosgene group, MSCs decreased the levels of TNF-α, IL-1β, and IL-6 and increased the levels of IL-10, HGF and SP-C. Different MSCs displayed no significant differences in proliferation. However, BMSCs showed the strongest migration ability. HGF increased the expressions of p-GSK-3β and β-catenin in MSCs. All MSCs exerted protective effects on phosgene-induced lung injury by reducing inflammation, immune regulation and restoring cell function. Conclusions BMSCs showed the best protective effects followed by hCMSCs and LRMSCs. HGF enhances the role of MSCs by activating the p-GSK-3β/β-catenin signaling pathway.

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“…LR-MSCs have become a hotspot in the field of pulmonary fibrosis research because of their potential for repair and differentiation [ 8 ]. The transformation of LR-MSCs into myofibroblasts lose the therapeutic effect of stem cells and induces IPF progression [ 9 , 10 ]. At present, the specific mechanism regulating the differentiation of LR-MSCs is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…MSCs have been found to reside in interstitial perivascular niches in the lung, these lung-resident mesenchymal stem cells (LR-MSCs) regulating the proliferation of myofibroblasts and possessing typical characteristics shared by other tissue-specific MSCs, including self-renewal ability [ 6 – 8 ]. If LR-MSCs differentiate into myofibroblasts, they will be unable to repair damaged lung tissue and secrete extracellular matrix components, such as collagen fibers, to accelerate pulmonary fibrosis [ 9 , 10 ]. Therefore, the transformation of LR-MSCs into myofibroblasts might underlie the progression of IPF.…”

Section: Introductionmentioning

confidence: 99%

SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression

Sun

Liu²,

Yang³

et al. 2022

Cell Commun Signal

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Background Lung resident mesenchymal stem cells (LR-MSCs) play an important role in idiopathic pulmonary fibrosis (IPF) by transforming into myofibroblasts, thereby losing their repair ability. Evidence suggests that key proteins of multiple signaling pathways are involved in myofibroblast differentiation of LR-MSCs, such as β-Catenin and GLI family zinc finger 1 (GLI1). These proteins are regulated by SUMO (small ubiquitin-like modifier) modification, which is a post-translational modification that promotes protein degradation, while Sumo specific protein 1 (SENP1)-mediated deSUMOylation produces the opposite biological effects. Therefore, we speculated that SENP1 might be a potential target for treating pulmonary fibrosis by preventing the myofibroblast differentiation of LR-MSCs. Methods LR-MSCs were isolated from mice by using immunomagnetic beads. The extracted LR-MSCs were identified by flow cytometric analysis and multilineage differentiation assays. Lentivirus packaged shRNA silenced the expression of SENP1 in vitro and vivo. The silencing efficacy of SENP1 was verified by real-time quantitative PCR. The effect of down-regulated SENP1 on the myofibroblast differentiation of LR-MSCs was assessed by Immunofluorescence and Western blot. Immunoprecipitation was used to clarify that SENP1 was a key target for regulating the activity of multiple signaling pathways in the direction of LR-MSCs differentiation. LR-MSCs resident in the lung was analyzed with in vivo imaging system. HE and Masson staining was used to evaluate the therapeutic effect of LR-MSCs with SENP1 down-regulation on the lung of BLM mice. Results In this study, we found that the myofibroblast differentiation of LR-MSCs in IPF lung tissue was accompanied by enhanced SENP1-mediated deSUMOylation. The expression of SENP1 increased in LR-MSCs transition of bleomycin (BLM)-induced lung fibrosis. Interfering with expression of SENP1 inhibited the transformation of LR-MSCs into myofibroblasts in vitro and in vivo and restored their therapeutic effect in BLM lung fibrosis. In addition, activation of the WNT/β-Catenin and Hedgehog/GLI signaling pathways depends on SENP1-mediated deSUMOylation. Conclusions SENP1 might be a potential target to restore the repair function of LR-MSCs and treat pulmonary fibrosis.

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Treatment of Hyperoxia-Induced Lung Injury with Lung Mesenchymal Stem Cells in Mice

Cited by 17 publications

References 30 publications

The Effects of Tyrosine-Protein Kinase Kit on Bronchopulmonary Dysplasia

The Effects of Tyrosine-Protein Kinase Kit on Bronchopulmonary Dysplasia

Comparison of the effects of different mesenchymal stem cells on attenuating phosgene-induced lung injury in rats

SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression

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