| Autor: |
Min Chen, Siyang Zuo, Siyu Chen, Xia Li, Tian Zhang, Dan Yang, Xue Zou, Yuan Yang, Hehua Long, Rui Peng, Huixiong Yuan, Bing Guo, Lirong Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 153, Iss 1, Pp 38-45 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2023.07.003 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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