Jingyuan Dai1, Mengchuan Xu1, Xiaoran Zhang1, Qiang Niu1, Yunhua Hu1, Yu Li1, Shugang Li2. 1. Department of Public Health, School of Medicine, Shihezi University, Shihezi 832000, Xinjiang, China. 2. Department of Public Health, School of Medicine, Shihezi University, Shihezi 832000, Xinjiang, China. Electronic address: lishugang@ymail.com.
Abstract
BACKGROUND: Arsenic exposure can cause fibrosis of organs including the liver, heart and lung. It was reported that TGF-β/Smad pathway played a crucial role in the process of fibrosis. However, the mechanism of arsenic-induced fibrosis through TGF-β/Smad signaling pathway has remained controversial. OBJECTIVE: A systematic review and meta-analysis was performed to clarify the relationship between arsenic and TGF-β/Smad pathway, providing a theoretical basis of fibrosis process caused by arsenic. METHODS: A meta-analysis was used to reveal a correlation between arsenic and fibrosis markers of TGF-β/Smad pathway, including 47 articles of both in vivo and in vitro studies. (Standardized Mean Difference) SMD was employed to compare and analyze the combined effects. When I2 > was 50%, random effect model was selected and subgroup analysis was used to explore the source of heterogeneity. RESULTS: Arsenic exposure up-regulated the expression of TGF-β1, p-Smad2/3, α-SMA, Collagen1/3 and FN. The dose-response relationship showed that low dose (≤5 μmol/L) arsenic exposure up-regulated the expression of TGF-β1, whereas high doses had a tendency to down-regulate that of TGF-β1. Subgroup analysis showed that low or short-term arsenic exposure induced the expression of TGF-β1 and fibrosis markers. CONCLUSION: The results indicated that arsenic activates the TGF-β/Smad pathway and induced fibrosis. The mechanism is related to the up-regulation of NADPH oxidase and ROS accumulation. However, high-dose arsenic exposure may inhibit this pathway.
BACKGROUND:Arsenic exposure can cause fibrosis of organs including the liver, heart and lung. It was reported that TGF-β/Smad pathway played a crucial role in the process of fibrosis. However, the mechanism of arsenic-induced fibrosis through TGF-β/Smad signaling pathway has remained controversial. OBJECTIVE: A systematic review and meta-analysis was performed to clarify the relationship between arsenic and TGF-β/Smad pathway, providing a theoretical basis of fibrosis process caused by arsenic. METHODS: A meta-analysis was used to reveal a correlation between arsenic and fibrosis markers of TGF-β/Smad pathway, including 47 articles of both in vivo and in vitro studies. (Standardized Mean Difference) SMD was employed to compare and analyze the combined effects. When I2 > was 50%, random effect model was selected and subgroup analysis was used to explore the source of heterogeneity. RESULTS:Arsenic exposure up-regulated the expression of TGF-β1, p-Smad2/3, α-SMA, Collagen1/3 and FN. The dose-response relationship showed that low dose (≤5 μmol/L) arsenic exposure up-regulated the expression of TGF-β1, whereas high doses had a tendency to down-regulate that of TGF-β1. Subgroup analysis showed that low or short-term arsenic exposure induced the expression of TGF-β1 and fibrosis markers. CONCLUSION: The results indicated that arsenic activates the TGF-β/Smad pathway and induced fibrosis. The mechanism is related to the up-regulation of NADPH oxidase and ROS accumulation. However, high-dose arsenic exposure may inhibit this pathway.
Authors: Anatoly V Skalny; Thania Rios Rossi Lima; Tao Ke; Ji-Chang Zhou; Julia Bornhorst; Svetlana I Alekseenko; Jan Aaseth; Ourania Anesti; Dimosthenis A Sarigiannis; Aristides Tsatsakis; Michael Aschner; Alexey A Tinkov Journal: Food Chem Toxicol Date: 2020-10-16 Impact factor: 6.023