Dataset Information

Adipose-derived stem cells therapy effectively attenuates PM_2.5-induced lung injury.

ABSTRACT:

Background

The adverse health effects of fine particulate matter (PM_2.5) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM_2.5-induced lung injury has not been investigated.

Method

C57BL/6 mice were exposed to PM_2.5 every other day via intratracheal instillation for 4 weeks. After that, the mice received tail vein injections of ADSCs every 2 weeks.

Results

ADSC transplantation significantly attenuated systemic and pulmonary inflammation, cardiac dysfunction, fibrosis, and cell death in PM_2.5-exposed mice. RNA-sequencing results and bioinformatic analysis suggested that the downregulated differentially expressed genes (DEGs) were mainly enriched in inflammatory and immune pathways. Moreover, ADSC transplantation attenuated PM_2.5-induced cell apoptosis and pyroptosis in the lungs and hearts.

Conclusion

ADSCs protect against PM_2.5-induced adverse health effects through attenuating pulmonary inflammation and cell death. Our findings suggest that ADSC transplantation may be a potential therapeutic approach for severe air pollution-associated diseases.

SUBMITTER: Gao J

PROVIDER: S-EPMC8214780 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Adipose-derived stem cells therapy effectively attenuates PM<sub>2.5</sub>-induced lung injury.

Gao Junling J Yuan Juntao J Liu Qun Q Wang Yuanli Y Wang Huiwen H Chen Yingjie Y Ding Wenjun W Ji Guangju G Lu Zhongbing Z

Stem cell research & therapy 20210619 1

<h4>Background</h4>The adverse health effects of fine particulate matter (PM<sub>2.5</sub>) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM<sub>2.5</sub>-induced lung injury has not been investigated.<h4>Method</h4>C57BL/6 mice were exposed to PM<sub>2.5</sub> every other day via intratrache ...[more]

PMID: 34147136

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Project description:BackgroundPM2.5 is a well-known harmful air pollutant that can lead to acute exacerbation and aggravation of respiratory diseases. Although ferroptosis is involves in the pathological process of pulmonary disease, the potential mechanism of ferroptosis in PM2.5-caused lung inflammation and fibrosis need to be further clarified. Quercetin is a phenolic compound that can inhibit ferroptosis in various diseases. Hence, this study explores the role of ferroptosis in lung injury induced by PM2.5 in order to further elucidate the beneficial effect of quercetin and its underlying mechanism.MethodsC57BL/6J mice were treated with either saline or PM2.5 by intratracheal instillation 20 times (once every two days). Additionally, PM2.5-treated mice were supplemented with two doses of quercetin. Lung injury, lipid peroxidation, iron content and ferroptosis marker protein expression and the Nrf2 signaling pathway were evaluated. In vitro, cell experiments were applied to verify the mechanisms underlying the links between Nrf2 signaling pathway activation and ferroptosis as well as between ferroptosis and inflammation.ResultsIn vivo, PM2.5 increased lung inflammation and caused lung fibrosis and increased lipid peroxidation contents, iron contents and ferroptosis markers in lung tissues; these effects were significantly reversed by quercetin. Additionally, quercetin upregulated the nuclear Nrf2 expression and downregulated Keap1 expression in lung tissues of PM2.5-exposed mice. Quercetin decreased lipid peroxidation products, iron contents and ferroptosis levels and increased the nuclear translocation of Nrf2 and the degradation of Keap1 in PM2.5-exposed BEAS-2B cells. Moreover, we found that quercetin and dimethyl fumarate markedly decreased lipid peroxidation production and ferroptosis by activating the Nrf2-Keap1 pathway in PM2.5-exposed cells. Furthermore, quercetin reduced inflammatory cytokines and TGF-β1 in PM2.5-exposed cells.ConclusionOur data suggested that Nrf2 is involved in ferroptosis in PM2.5-induced lung injury, and quercetin can alleviate these adverse effects via activating Nrf2-Keap1 signaling pathway.

Project description:BackgroundAirborne 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.MethodsDdah1-/- 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.ResultsDdah1-/- 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.ConclusionOur data revealed that DDAH1 has a marked protective effect on long-term PM2.5 exposure-induced lung injury.

Dataset Information

Adipose-derived stem cells therapy effectively attenuates PM_2.5-induced lung injury.

Background

Method

Results

Conclusion

Publications

Adipose-derived stem cells therapy effectively attenuates PM<sub>2.5</sub>-induced lung injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

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

Background

Method

Results

Conclusion

Publications

Adipose-derived stem cells therapy effectively attenuates PM<sub>2.5</sub>-induced lung injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Adipose-derived stem cells therapy effectively attenuates PM_2.5-induced lung injury.