TY - JOUR
T1 - Effects of sub-chronic exposure to atmospheric PM2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats
AU - Li, Ruijin
AU - Zhang, Mei
AU - Wang, Ying
AU - YUNG, Kin Lam
AU - Su, Ruijun
AU - Li, Zhuoyu
AU - Zhao, Liping
AU - Dong, Chuan
AU - CAI, Zongwei
N1 - Funding Information:
This research was supported by the National Natural Science Foundation of China (No. 91543202 and 21575084), HKBU Strategic Development Fund (No. 15-1012-P04), and 100 talents program of Shanxi Province of China.
PY - 2018/3
Y1 - 2018/3
N2 - Epidemiological studies have revealed that exposure to PM2.5 is linked to liver cancer. However, the hepatic toxicity and relevant molecular mechanisms of PM2.5 have not yet been fully described. Herein, we report on our investigation of the fibrosis, inflammation, endoplasmic reticulum (ER) stress and apoptosis in the livers of rats, caused by exposure to PM2.5 during summer and winter in Taiyuan, China. Male SD rats were sub-chronically exposed to PM2.5 (in summer: 0.2, 0.6, 1.5 mg per kg of b.w.; in winter: 0.3, 1.5, 2.7 mg per kg of b.w.) via intratracheal instillation once every 3 days for 60 days. The results showed that exposure to high dosages of PM2.5 caused the following: (1) hepatic histopathological changes and liver function decline through elevating the activities of AST, ALT, CYP450 and GST; (2) triggered liver fibrosis, in which TGF-β1, Col I, Col III, and MMP13 mRNA and protein expression were significantly upregulated, and enhanced inflammation with the overexpression of TNF-α, IL-6 and HO-1 versus the control; (3) induced liver ER stress and cell apoptosis via activating the GRP78/ATF6/CHOP/TRB3/caspase 12 pathway. The data also indicated that the liver injury induced by winter PM2.5 in Taiyuan was more serious compared to that induced by summer PM2.5. This work provides new insight into the mechanisms of PM2.5-induced liver injury, and aids the understanding of the underlying mechanisms by which PM2.5 might affect liver diseases.
AB - Epidemiological studies have revealed that exposure to PM2.5 is linked to liver cancer. However, the hepatic toxicity and relevant molecular mechanisms of PM2.5 have not yet been fully described. Herein, we report on our investigation of the fibrosis, inflammation, endoplasmic reticulum (ER) stress and apoptosis in the livers of rats, caused by exposure to PM2.5 during summer and winter in Taiyuan, China. Male SD rats were sub-chronically exposed to PM2.5 (in summer: 0.2, 0.6, 1.5 mg per kg of b.w.; in winter: 0.3, 1.5, 2.7 mg per kg of b.w.) via intratracheal instillation once every 3 days for 60 days. The results showed that exposure to high dosages of PM2.5 caused the following: (1) hepatic histopathological changes and liver function decline through elevating the activities of AST, ALT, CYP450 and GST; (2) triggered liver fibrosis, in which TGF-β1, Col I, Col III, and MMP13 mRNA and protein expression were significantly upregulated, and enhanced inflammation with the overexpression of TNF-α, IL-6 and HO-1 versus the control; (3) induced liver ER stress and cell apoptosis via activating the GRP78/ATF6/CHOP/TRB3/caspase 12 pathway. The data also indicated that the liver injury induced by winter PM2.5 in Taiyuan was more serious compared to that induced by summer PM2.5. This work provides new insight into the mechanisms of PM2.5-induced liver injury, and aids the understanding of the underlying mechanisms by which PM2.5 might affect liver diseases.
UR - http://www.scopus.com/inward/record.url?scp=85042928801&partnerID=8YFLogxK
U2 - 10.1039/c7tx00262a
DO - 10.1039/c7tx00262a
M3 - Journal article
AN - SCOPUS:85042928801
SN - 2045-452X
VL - 7
SP - 271
EP - 282
JO - Toxicology Research
JF - Toxicology Research
IS - 2
ER -
