Role of DNA dioxygenase TET1 in cardiac fibrosis induced by high pressure
- Author:
Lu-An LI
1
;
Qing-Rui WU
1
;
Qian LI
1
;
Fang RAO
1
;
Bin ZHANG
1
;
Lu-An LI
2
;
Qian LI
2
;
Qian-Huan ZHANG
2
;
Bin ZHANG
2
;
Qing-Rui WU
3
;
Fang RAO
3
;
Su-Juan KUANG
3
;
Hui YANG
3
Author Information
- Publication Type:Journal Article
- Keywords: 5-hmC; cardiac fibrosis; demethylation; high pressure; TET1; TGF-β
- From: Chinese Pharmacological Bulletin 2021;37(7):922-928
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the mechanism of TET1 in cardiac fibrosis induced by high pressure. Methods Wistar rats and spontaneous hypertension rats(SHR) were selected to detected the expression of TET1, TGF-β, COL-1 and COL-3 in myocardium by Western blot; HE and Masson staining were used to detect myocardial pathological changes. Neonatal rat cardiac fibroblasts (NRCFs) were isolated from the ventricles of neonatal Sprague-Dawley rats and stimulated by 0 mm-Hg, 120 mmHg and 180 mmHg high pressure. Immunofluorescence was used to detect the changes of 5-hmC in the NRCFs. The changes of 5-hmC and 5-mC in TGF-β promoter region were detected by qRT-PCR. The expressions of TET1, TGF-β, COL-1 and COL-3 were detected by Western blot. Results Compared with Wistar rats, SHR showed increased blood pressure, increased fibrous collagen in ventricular tissues, and significantly increased expressions of TET1, TGF-P, COL-1 and COL-3. Compared with the 0 mmHg group, 120 mmHg and 180 mmHg group significantly induced the increase of TET1, 5-hmC, TGF-p, COL-1 and COL-3. TET1 knockdown significantly reduced the increase of 5-hmC, TGF-β, COL-1 and COL-3 under 180 mmHg pressure. Besides, knockdown TET1 significantly reduced the level of 5-hmC and increased the level of 5-mC and 5-hmC in the TGF-β promoter region. Conclusions High pressure induced cardiac fibrosis is associated with the promotion of TGF-β promoter demethylation and the increased of TGF-β expression by TET1.
