Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells

Chirino, Yolanda I.; García-Cuéllar, Claudia M.; García-García, Carlos; Soto-Reyes, Ernesto; Osornio-Vargas, Álvaro; López-Saavedra, Alejandro; Miranda, J.; Quintana-Belmares, Raúl; Pérez, Isaac Enríquez; Sánchez-Pérez, Yesennia

doi:10.1016/j.toxlet.2017.03.002

Cited by 36 publications

(18 citation statements)

References 31 publications

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“…We extensively report that PM 2.5 is able to determine significant modifications in the cell cytoskeleton, such as loss of stress fibers, modified actin structure, and increased membrane ruffling [54,58]. These data are supported by a recent publication by Chirino and colleagues [59]. These alterations were related to a significant relocation of cadherin-1 and increased serpin-2 expression and heat shock protein 27 (HSP27) phosphorylation [58,60].…”

Section: Fine Pm (Pm 25 )mentioning

confidence: 66%

Fifteen Years of Airborne Particulates in Vitro Toxicology in Milano: Lessons and Perspectives Learned

Longhin

Mantecca

Gualtieri

2020

IJMS

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Air pollution is one of the world’s leading environmental causes of death. The epidemiological relationship between outdoor air pollution and the onset of health diseases associated with death is now well established. Relevant toxicological proofs are now dissecting the molecular processes that cause inflammation, reactive species generation, and DNA damage. In addition, new data are pointing out the role of airborne particulates in the modulation of genes and microRNAs potentially involved in the onset of human diseases. In the present review we collect the relevant findings on airborne particulates of one of the biggest hot spots of air pollution in Europe (i.e., the Po Valley), in the largest urban area of this region, Milan. The different aerodynamic fractions are discussed separately with a specific focus on fine and ultrafine particles that are now the main focus of several studies. Results are compared with more recent international findings. Possible future perspectives of research are proposed to create a new discussion among scientists working on the toxicological effects of airborne particles.

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Section: Fine Pm (Pm 25 )mentioning

confidence: 66%

Fifteen Years of Airborne Particulates in Vitro Toxicology in Milano: Lessons and Perspectives Learned

Longhin

Mantecca

Gualtieri

2020

IJMS

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“…160 µg/ml of CLB2.0 could not affect the expression of inflammatory cytokines, but cytotoxicity did. Chirono et al reported that PM10 induced cytoskeleton remodeling in A549 cells [5]. Thus, we hypothesized that CLB2.0 could also produce similar effects.…”

Section: Clb20 Increased F-actin Formation and Decreased Transepithementioning

confidence: 81%

Down-regulation of Fine Dusts-induced Airway Inflammation by the PDZ motif peptide of ZO-1

Kang

Lee²,

Kim

et al. 2020

Preprint

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BACKGROUND: Although fine airborne particulate matter (PM) has been known to play a role in many human diseases, there is no direct evidence that therapeutic drugs or proteins can diminish PM-induced diseases. Nevertheless, studies examining the negative control mechanisms of PM-induced diseases are critical to develop novel therapeutic medications. RESULTS: We found that CLB2.0, a surrogate for PM, induced production of multiple cytokines that alter airway inflammation. Interestingly, deletion of each PDZ domain in the ZO-1 protein dramatically decreased F-actin formation and increased the expression of genes for pro-inflammatory cytokines. We also found that the consensus PDZ peptide in ZO-1 downregulates the expression of pro-inflammatory cytokine genes and F-actin formation; in contrast, the GG24,25AA mutant PDZ peptide upregulates them. Moreover, CLB2.0-induced F-actin formation in 2D and 3D matrix cultures was significantly inhibited by PDZ peptide, but not by the mutant peptide. Induction of IL-8 secretion by CLB2.0 activates CXCR2 signaling, while increased RGS12 controlled by the PDZ peptide inhibits IL-8/CXCR2 signaling. The consensus PDZ peptide also inhibited CLB2.0-induced inflammatory cell infiltration, pro-inflammatory cytokine gene expression, and TEER in bronchoalveolar lavage (BAL) fluid and AM cells. CONCLUSIONS: Our data indicated that the PDZ domain in ZO-1 is critical for regulation of the CLB2.0-induced inflammatory microenvironment. Therefore, we suggest that the PDZ peptide may be a potential therapeutic candidate during PM-induced respiratory diseases.

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“…Wound healing and tissue repair are a multi-step process composed of wound sensing and blocking, plasma membrane restorage, and cytoskeleton remodeling. Although the detailed wound healing mechanism is not clear yet, it is reported to be tightly controlled by Rho family GTPase pathways, including RhoA/Rock, Rac and Cdc42 signalings (43)(44)(45). In our model, the Rhoa/Rock-mediated actomyosin contraction was activated in response to the prolonged exposure to PM 1 by the upregulated Ga4, Itgb1, Cd14 proteins and the increased levels of intracellular Ca 2+ and mTORC2 complex, suggesting a repair initiation for membrane resealing and wound closure.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Exposure to Traffic-related Particulate Matter Showed Distinct Molecular Mechanisms of Lung Injury in Rats

Jheng¹,

Putri²,

Chuang³

et al. 2020

Preprint

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Background: Exposure to particulate matter (PM) pollution has direct impacts on the respiratory organs, yet the molecular alterations underlying PM-induced pulmonary injury remain unclear. In this study, we investigated the effect of PM on lung tissues of SD rats with whole-body exposure to traffic-related PM1 (< 1 mm in aerodynamic diameter) pollutants and compared it with rats exposed to high-efficiency particulate air-filtered gaseous pollutants and clean air control for 3 and 6 months. Lung function and histological examinations as well as quantitative proteomics analysis and functional validation were performed. Results: The rats in 6-month PM1-exposed group showed significant decline in lung function by decreased forced expiratory flow and forced expiratory volume, but the histological analysis revealed an earlier lung damage evidenced by increased congestion and macrophage infiltration in 3-month PM1-exposed rat lungs. The lung tissue proteomics analysis identified 2,673 proteins which highlighted dysregulations on proteins involved in oxidative stress, cellular metabolisms, calcium signaling, inflammatory responses, and actin dynamics. The presence of fine particles specifically enhanced the oxidative stress and inflammatory reactions under sub-chronic exposure of traffic-related PM1 and suppressed the glucose metabolism and actin cytoskeleton signaling which might lead to repair failure and thus lung function decline after chronic exposure of traffic-related PM1. A detailed pathogenic mechanism was proposed to depict the temporal and dynamic molecular regulations associated with PM1-induced lung injury.Conclusion: Our study explored the earlier lung injury prior to lung function decline and proposed potential molecular features for traffic-related PM1-induced lung injury.

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Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells

Cited by 36 publications

References 31 publications

Fifteen Years of Airborne Particulates in Vitro Toxicology in Milano: Lessons and Perspectives Learned

Fifteen Years of Airborne Particulates in Vitro Toxicology in Milano: Lessons and Perspectives Learned

Down-regulation of Fine Dusts-induced Airway Inflammation by the PDZ motif peptide of ZO-1

Prolonged Exposure to Traffic-related Particulate Matter Showed Distinct Molecular Mechanisms of Lung Injury in Rats

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