J Pharmacol Sci
Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China; Guizhou Precision Medicine Institute, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China. Electronic address:
Published: September 2023
SET and MYND domain protein 2 (SMYD2) can methylate histone H3 at lysine36 (H3K36) and some non-histone substrates to play a role in tumorigenesis. However, It is unclear how SMYD2 contributes to chronic kidney disease (CKD). Here, AZ505 or LLY507, which could inhibit SMYD2, were used in cisplatin-induced CKD to investigate the effects and possible mechanisms by which they might act. We found that high expression of SMYD2 in cisplatin-induced CKD. However, AZ505 or LLY507 can significantly inhibit its expression, improve renal function injury and fibrosis induced by cisplatin, inhibit the transition of epithelial cells to a fibrogenic phenotype and fibrosis-related proteins, inhibit the expression of Inflammatory Cytokines (such as IL-6 and TNF-α), And inhibit the phosphorylation of pro-fibrosis molecule Smad3 and signal transduction and transcription activator-3 (STAT3) and up-regulated the expression of renal protective factor Smad7. In cultured tubular epithelial cells, AZ505 also can inhibit the expression of EMT, fibrosis-related proteins, and inflammatory cytokines in cisplatin-induced tubular epithelial cells. Based on these findings, SMYD2 may be a critical regulator of cisplatin-induced CKD and targeted pharmacological inhibition of SMYD2 may prevent cisplatin-induced CKD through Smad3 or STAT3-related signaling pathways.
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http://dx.doi.org/10.1016/j.jphs.2023.07.003 | DOI Listing |
Int Immunopharmacol
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Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing 210008 China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing 210008 China; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing 210029 China. Electronic address:
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Department of Food Nutrition and Healthy Biotechnology, College of Medical and Health Sciences, Asia University, Taichung 413, Taiwan.
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Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt. Electronic address:
Chem Biol Interact
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Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. Electronic address:
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