Bi-directional regulation of TGF-β/Smad pathway by arsenic: A systemic review and meta-analysis of in vivo and in vitro studies
| Autor: | Mengchuan Xu, Shugang Li, Yu Li, Xiaoran Zhang, Qiang Niu, Jingyuan Dai, Yunhua Hu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Liver Cirrhosis
0301 basic medicine chemistry.chemical_element Smad Proteins SMAD 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Arsenic 03 medical and health sciences 0302 clinical medicine Transforming Growth Factor beta In vivo Fibrosis medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics NADPH oxidase Lung biology Chemistry NADPH Oxidases General Medicine medicine.disease In vitro 030104 developmental biology medicine.anatomical_structure Liver Cancer research biology.protein Signal transduction Reactive Oxygen Species Signal Transduction |
| Zdroj: | Life Sciences. 220:92-105 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2019.01.042 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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