Phospholipase D1 Ameliorates Apoptosis in Chronic Renal Toxicity Caused by Low-Dose Cadmium Exposure
| Autor: | Wenya Yuan, Yaotang Deng, Fei Zou, Guanghai Wang, Ke Huang, Jian Geng |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Necrosis Article Subject Cell Survival Apoptosis 010501 environmental sciences Kidney 01 natural sciences General Biochemistry Genetics and Molecular Biology Cell Line Nephrotoxicity Rats Sprague-Dawley 03 medical and health sciences Phospholipase D medicine Animals Renal Insufficiency 3' Untranslated Regions Chronic toxicity Cell Proliferation 0105 earth and related environmental sciences General Immunology and Microbiology Chemistry Kidney metabolism General Medicine Rats MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Toxicity Cancer research Medicine medicine.symptom Phospholipase D1 Cadmium Research Article |
| Zdroj: | BioMed Research International, Vol 2020 (2020) BioMed Research International |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2020/7091053 |
| Popis: | Exposure to cadmium (Cd), a common heavy metal used in industry, can result in long-term chronic toxicity. It has been well characterized that kidneys are the main organs that are targeted by toxicity, which can cause apoptosis, necrosis, and atrophy of renal tubular epithelial cells. However, the molecular mechanisms associated with Cd toxicity remain unclear. In this study, the expression of renal proteins in Sprague-Dawley rats exposed to chronic Cd was analyzed with iTRAQ proteomics. Bioinformatics analysis indicated that phospholipase D1 (PLD1) was significantly underexpressed and may correlate strongly with Cd-induced chronic kidney impairment. Previous studies have shown that PLD1 promotes cell proliferation and inhibits apoptosis, indicating that PLD1 may be implicated in the pathogenesis of kidney injury induced by Cd. Studies in vivo and in vitro all demonstrate that the mRNA and protein levels of PLD1 decrease significantly both in kidney tissue and in proximal tubular cell lines exposed to Cd. Overexpression of PLD1 and its downstream product PA could ameliorate Cd-induced apoptosis. Moreover, we identified that miR-122-5p was a regulatory miRNA of PLD1. miR-122-5p was overexpressed after Cd exposure and promoted cell apoptosis by downregulating PLD1 through binding the 3′UTR of the locus at 1761–1784 nt. In conclusion, our results indicated that PLD1 and its downstream PA were strongly implicated in Cd-induced chronic kidney impairment and could be a novel player in the defense against Cd-induced nephrotoxicity. |
| Databáze: | OpenAIRE |
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