Adipose-derived stem cells therapy effectively attenuates PM2.5-induced lung injury

Gao, Junling; Yuan, Jun-Tao; Li, Qun; Wang, Yuanli; Wang, Huiwen; Chen, Yingjie; Ding, Wenjun; Ji, Guangju; Lu, Zhigang

doi:10.1186/s13287-021-02441-3

Cited by 9 publications

(5 citation statements)

References 49 publications

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“…As described previously [ 49 ], lung paraffin Sects. (5 μm) were stained with H&E, Masson’s trichrome staining kits, DHE, specific antibodies and TUNEL kits.…”

Section: Methodsmentioning

confidence: 99%

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Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress

et al. 2022

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Background Airborne fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) pollution is associated with the prevalence of respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease. In patients with those diseases, circulating asymmetric dimethylarginine (ADMA) levels are increased, which contributes to airway nitric oxide deficiency, oxidative stress and inflammation. Overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme degrading ADMA, exerts protective effects in animal models. However, the impact of DDAH1/ADMA on PM2.5-induced lung injury has not been investigated. Methods Ddah1−/− and DDAH1-transgenic mice, as well as their respective wild-type (WT) littermates, were exposed to either filtered air or airborne PM2.5 (mean daily concentration ~ 50 µg/m3) for 6 months through a whole-body exposure system. Mice were also acutely exposed to 10 mg/kg PM2.5 and/or exogenous ADMA (2 mg/kg) via intratracheal instillation every other day for 2 weeks. Inflammatory response, oxidative stress and related gene expressions in the lungs were examined. In addition, RAW264.7 cells were exposed to PM2.5 and/or ADMA and the changes in intracellular oxidative stress and inflammatory response were determined. Results Ddah1−/− mice developed more severe lung injury than WT mice after long-term PM2.5 exposure, which was associated with greater induction of pulmonary oxidative stress and inflammation. In the lungs of PM2.5-exposed mice, Ddah1 deficiency increased protein expression of p-p65, iNOS and Bax, and decreased protein expression of Bcl-2, SOD1 and peroxiredoxin 4. Conversely, DDAH1 overexpression significantly alleviated lung injury, attenuated pulmonary oxidative stress and inflammation, and exerted opposite effects on those proteins in PM2.5-exposed mice. In addition, exogenous ADMA administration could mimic the effect of Ddah1 deficiency on PM2.5-induced lung injury, oxidative stress and inflammation. In PM2.5-exposed macrophages, ADMA aggravated the inflammatory response and oxidative stress in an iNOS-dependent manner. Conclusion Our data revealed that DDAH1 has a marked protective effect on long-term PM2.5 exposure-induced lung injury.

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“…As described previously [ 49 ], lung paraffin Sects. (5 μm) were stained with H&E, Masson’s trichrome staining kits, DHE, specific antibodies and TUNEL kits.…”

Section: Methodsmentioning

confidence: 99%

“…The detailed protocols for cDNA synthesis, quantitative real-time PCR, protein extraction and Western blots were described previously [ 49 ]. The primary antibodies and primers used in this study are listed in Additional file 2 : Table S6 and Additional file 2 : Table S7, respectively.…”

Section: Methodsmentioning

confidence: 99%

Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress

et al. 2022

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“…A promising strategy for the treatment of liver diseases is based on the application of stem cells or their secretions [ 17 – 19 ]. Among all stem cells, mesenchymal stem cells (MSCs) are characterized by their self-renewal potential and differentiation ability, leading to a good application in disease treatment [ 20 , 21 ]. The therapeutic effect of MSCs mainly relies on paracrine signaling, differentiation, and inflammatory actions [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice

Guo²,

Zhang

et al. 2021

Stem Cell Res Ther

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Background Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic disease. Its incidence is associated with type 2 diabetes mellitus (T2DM). Presently, there is no approved pharmacological agents specially developed for NAFLD. One promising disease-modifying strategy is the transplantation of stem cells to promote metabolic regulation and repair of injury. Method In this study, a T2DM model was established through 28-week high-fat diet (HFD) feeding resulting in T2DM-associated NAFLD, followed by the injection of bone marrow mesenchymal stem cells (BMSCs). The morphology, function, and transfer of hepatocyte mitochondria were evaluated in both vivo and in vitro. Results BMSC implantation resulted in the considerable recovery of increasing weight, HFD-induced steatosis, liver function, and disordered glucose and lipid metabolism. The treatment with BMSC transplantation was accompanied by reduced fat accumulation. Moreover, mitochondrial transfer was observed in both vivo and vitro studies. And the mitochondria-recipient steatotic cells exhibited significantly enhanced OXPHOS activity, ATP production, and mitochondrial membrane potential, and reduced reactive oxygen species levels, which were not achieved by the blocking of mitochondrial transfer. Conclusion Mitochondrial transfer from BMSCs is a feasible process to combat NAFLD via rescuing dysfunction mitochondria, and has a promising therapeutic effect on metabolism-related diseases.

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“…After purification with DNase I and an rRNA Removal Kit (Human/Mouse/Rat) (Illumina, San Diego, CA, USA), a BGISEQ500 platform was used for library construction and RNA sequencing (BGI-Shenzhen, China). The detailed protocol/software for raw data reading, cleaning, mapping, gene expression level assessment, differentially expressed gene (DEG) screening and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were described in our previous reports [ 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Inhibition of GCN2 Alleviates Cardiomyopathy in Type 2 Diabetic Mice via Attenuating Lipotoxicity and Oxidative Stress

Yuan

Cui

et al. 2022

Antioxidants

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Diabetic cardiomyopathy (DCM) is a kind of heart disease that affects diabetic patients and is one of the primary causes of death. We previously demonstrated that deletion of the general control nonderepressible 2 (GCN2) kinase ameliorates cardiac dysfunction in diabetic mice. The aim of this study was to investigate the protective effect of GCN2iB, a GCN2 inhibitor, in type 2 diabetic (T2D) mice induced by a high-fat diet (HFD) plus low-dose streptozotocin (STZ) treatments or deletion of the leptin receptor (db/db). GCN2iB (3 mg/kg/every other day) treatment for 6 weeks resulted in significant decreases in fasting blood glucose levels and body weight and increases in the left ventricular ejection fraction. GCN2iB treatment also attenuated myocardial fibrosis, lipid accumulation and oxidative stress in the hearts of T2D mice, which was associated with decreases in lipid metabolism-related genes and increases in antioxidative genes. Untargeted metabolomics and RNA sequencing analysis revealed that GCN2iB profoundly affected myocardial metabolomic profiles and gene expression profiles. In particular, GCN2iB increased myocardial phosphocreatine and taurine levels and upregulated genes involved in oxidative phosphorylation. In conclusion, the data provide evidence that GCN2iB effectively protects against cardiac dysfunction in T2D mice. Our findings suggest that GCN2iB might be a novel drug candidate for DCM therapy.

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Adipose-derived stem cells therapy effectively attenuates PM2.5-induced lung injury

Cited by 9 publications

References 49 publications

Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress

Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress

Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice

Inhibition of GCN2 Alleviates Cardiomyopathy in Type 2 Diabetic Mice via Attenuating Lipotoxicity and Oxidative Stress

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