Colonic Injuries Induced by Inhalational Exposure to Particulate-Matter Air Pollution

Xiaobo Li; Jian Cui; Hongbao Yang; Hao Sun; Runze Lu; Na Gao; Qingtao Meng; Shenshen Wu; Jiong Wu; Michael Aschner; Rui Chen

doi:10.1002/advs.201900180

Colonic Injuries Induced by Inhalational Exposure to Particulate-Matter Air Pollution

Xiaobo Li, Jian Cui, Hongbao Yang, Hao Sun, Runze Lu, Na Gao, Qingtao Meng, Shenshen Wu, Jiong Wu, Michael Aschner, Rui Chen

Molecular Pharmacology

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Particulate matter (PM) exposure has been associated with intestinal disorders. Therefore, there is an urgent need to understand the precise molecular mechanism involved and explore potential prevention strategies. In this study, inhaled PM is shown to activate inflammatory pathways in murine colon. In a panel study, it is found that ambient PM levels are significantly associated with elevated number of fecal white blood cells in healthy subjects. Acting as a promoter, PM exposure accelerates chemical carcinogenesis-induced colonic tumor formation in a murine model. Mechanistically, RNA-seq assays suggest activation of phosphoinositide 3-kinase (PI3K)/AKT cascades in chronically PM-exposed human colon mucosal epithelial cells. Ablation of up-stream driver fibroblast growth factor receptor 4 (FGFR4) effectively inhibits inflammation and neoplasia in PM-exposed murine colons. Notably, dietary curcumin supplement is shown to protect against PM-induced colonic injuries in mice. Collectively, these findings identify that PM exposure accelerates colonic tumorigenesis in a PI3K/AKT-dependent manner and suggests potential nutrient supplement for prevention.

Original language	English (US)
Article number	1900180
Journal	Advanced Science
Volume	6
Issue number	11
DOIs	https://doi.org/10.1002/advs.201900180
State	Published - Jun 5 2019

Keywords

colon
curcumin
inflammation
particulate matter

ASJC Scopus subject areas

Medicine (miscellaneous)
Chemical Engineering(all)
Materials Science(all)
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Engineering(all)
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/advs.201900180

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title = "Colonic Injuries Induced by Inhalational Exposure to Particulate-Matter Air Pollution",

abstract = "Particulate matter (PM) exposure has been associated with intestinal disorders. Therefore, there is an urgent need to understand the precise molecular mechanism involved and explore potential prevention strategies. In this study, inhaled PM is shown to activate inflammatory pathways in murine colon. In a panel study, it is found that ambient PM levels are significantly associated with elevated number of fecal white blood cells in healthy subjects. Acting as a promoter, PM exposure accelerates chemical carcinogenesis-induced colonic tumor formation in a murine model. Mechanistically, RNA-seq assays suggest activation of phosphoinositide 3-kinase (PI3K)/AKT cascades in chronically PM-exposed human colon mucosal epithelial cells. Ablation of up-stream driver fibroblast growth factor receptor 4 (FGFR4) effectively inhibits inflammation and neoplasia in PM-exposed murine colons. Notably, dietary curcumin supplement is shown to protect against PM-induced colonic injuries in mice. Collectively, these findings identify that PM exposure accelerates colonic tumorigenesis in a PI3K/AKT-dependent manner and suggests potential nutrient supplement for prevention.",

keywords = "colon, curcumin, inflammation, particulate matter",

author = "Xiaobo Li and Jian Cui and Hongbao Yang and Hao Sun and Runze Lu and Na Gao and Qingtao Meng and Shenshen Wu and Jiong Wu and Michael Aschner and Rui Chen",

note = "Funding Information: R.C. and X.L. conceived the study. X.L., J.C., H.Y., H.S., R.L., and Q.M. performed the experiments. N.G., S.W., and J.W. performed the bioinformation and statistical analysis. X.L., M.A., and R.C. wrote the manuscript, prepared the figures, and discussed the results and research directions. All authors approved the manuscript. R.C. was financially supported by the National Key R&D Program of China (2017YFC0211600 and 2017YFC0211603), the State Key Program of the National Natural Science Foundation of China (81730088), the Major Research Plan of the National Natural Science Foundation (training program) of China (91643109), Fund of International Cooperation and Exchange of the National Natural Science Foundation of China (81861138017), the Thousand Talent Program for Young Outstanding Scientists. X.L. was supported by the Major Research Plan of the National Natural Science Foundation (training program) of China (91743112). S.W. was supported by the Fundamental Research Funds for the Central Universities and the Postgraduate Research and Practice Innovation Program of Jiangsu Province, China (KYCX17_0187). M.A. was supported in part by grants from the National Institute of Environmental Health Sciences (NIEHS), USA (R01 ES10563, R01 ES07331 and R01 ES020852). Publisher Copyright: {\textcopyright} 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2019",

month = jun,

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doi = "10.1002/advs.201900180",

language = "English (US)",

volume = "6",

journal = "Advanced Science",

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T1 - Colonic Injuries Induced by Inhalational Exposure to Particulate-Matter Air Pollution

AU - Li, Xiaobo

AU - Cui, Jian

AU - Yang, Hongbao

AU - Sun, Hao

AU - Lu, Runze

AU - Gao, Na

AU - Meng, Qingtao

AU - Wu, Shenshen

AU - Wu, Jiong

AU - Aschner, Michael

AU - Chen, Rui

N1 - Funding Information: R.C. and X.L. conceived the study. X.L., J.C., H.Y., H.S., R.L., and Q.M. performed the experiments. N.G., S.W., and J.W. performed the bioinformation and statistical analysis. X.L., M.A., and R.C. wrote the manuscript, prepared the figures, and discussed the results and research directions. All authors approved the manuscript. R.C. was financially supported by the National Key R&D Program of China (2017YFC0211600 and 2017YFC0211603), the State Key Program of the National Natural Science Foundation of China (81730088), the Major Research Plan of the National Natural Science Foundation (training program) of China (91643109), Fund of International Cooperation and Exchange of the National Natural Science Foundation of China (81861138017), the Thousand Talent Program for Young Outstanding Scientists. X.L. was supported by the Major Research Plan of the National Natural Science Foundation (training program) of China (91743112). S.W. was supported by the Fundamental Research Funds for the Central Universities and the Postgraduate Research and Practice Innovation Program of Jiangsu Province, China (KYCX17_0187). M.A. was supported in part by grants from the National Institute of Environmental Health Sciences (NIEHS), USA (R01 ES10563, R01 ES07331 and R01 ES020852). Publisher Copyright: © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/6/5

Y1 - 2019/6/5

N2 - Particulate matter (PM) exposure has been associated with intestinal disorders. Therefore, there is an urgent need to understand the precise molecular mechanism involved and explore potential prevention strategies. In this study, inhaled PM is shown to activate inflammatory pathways in murine colon. In a panel study, it is found that ambient PM levels are significantly associated with elevated number of fecal white blood cells in healthy subjects. Acting as a promoter, PM exposure accelerates chemical carcinogenesis-induced colonic tumor formation in a murine model. Mechanistically, RNA-seq assays suggest activation of phosphoinositide 3-kinase (PI3K)/AKT cascades in chronically PM-exposed human colon mucosal epithelial cells. Ablation of up-stream driver fibroblast growth factor receptor 4 (FGFR4) effectively inhibits inflammation and neoplasia in PM-exposed murine colons. Notably, dietary curcumin supplement is shown to protect against PM-induced colonic injuries in mice. Collectively, these findings identify that PM exposure accelerates colonic tumorigenesis in a PI3K/AKT-dependent manner and suggests potential nutrient supplement for prevention.

AB - Particulate matter (PM) exposure has been associated with intestinal disorders. Therefore, there is an urgent need to understand the precise molecular mechanism involved and explore potential prevention strategies. In this study, inhaled PM is shown to activate inflammatory pathways in murine colon. In a panel study, it is found that ambient PM levels are significantly associated with elevated number of fecal white blood cells in healthy subjects. Acting as a promoter, PM exposure accelerates chemical carcinogenesis-induced colonic tumor formation in a murine model. Mechanistically, RNA-seq assays suggest activation of phosphoinositide 3-kinase (PI3K)/AKT cascades in chronically PM-exposed human colon mucosal epithelial cells. Ablation of up-stream driver fibroblast growth factor receptor 4 (FGFR4) effectively inhibits inflammation and neoplasia in PM-exposed murine colons. Notably, dietary curcumin supplement is shown to protect against PM-induced colonic injuries in mice. Collectively, these findings identify that PM exposure accelerates colonic tumorigenesis in a PI3K/AKT-dependent manner and suggests potential nutrient supplement for prevention.

KW - colon

KW - curcumin

KW - inflammation

KW - particulate matter

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U2 - 10.1002/advs.201900180

DO - 10.1002/advs.201900180

M3 - Article

AN - SCOPUS:85064048609

SN - 2198-3844

VL - 6

JO - Advanced Science

JF - Advanced Science

IS - 11

M1 - 1900180

ER -

Colonic Injuries Induced by Inhalational Exposure to Particulate-Matter Air Pollution

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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