Tea polyphenols delays human glomerular mesangial cells senescence induced by high glucose via regulating STAT3/miR-126/telomere signaling pathway activation.
10.19540/j.cnki.cjcmm.20181031.003
- Author:
Dong-Wei CAO
1
;
Wen-Bei HAN
2
;
Jin-Song HE
3
;
Min ZHAO
3
;
Chun-Ming JIANG
3
;
Qing-Yan ZHANG
3
;
Cheng WAN
3
;
Jing LIU
3
;
Yuan FENG
3
;
Bo JIN
3
;
Bo YANG
4
;
Da-Long ZHU
5
;
Xiao HAN
6
Author Information
1. Department of Nephrology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.
2. Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Chinese Medicine and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.
3. Department of Nephrology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
4. Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
5. Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.
6. Nanjing Medical University, Basic Medical School, Nanjing 210000, China.
- Publication Type:Journal Article
- Keywords:
STAT3;
diabetic kidney disease;
human glomerular mesangial cells senescence;
miR-126;
tea polyphenols;
telomere
- MeSH:
Cells, Cultured;
Cellular Senescence;
Cyclin-Dependent Kinase Inhibitor p21;
Glucose;
Humans;
Mesangial Cells;
MicroRNAs;
Polyphenols;
STAT3 Transcription Factor;
Tea;
Telomere;
Tumor Suppressor Protein p53
- From:
China Journal of Chinese Materia Medica
2018;43(23):4678-4684
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this paper was to explore the effects and possible mechanisms in vitro of tea polyphenols (TP) delaying human glomerular mesangial cells (HGMCs) senescence induced by high glucose (HG). HGMCs were cultured in vitro and divided into the normal group (N, 5.5 mmol·L⁻¹ glucose), the mannitol group(MNT, 5.5 mmol·L⁻¹ glucose plus 24.5 mmol·L⁻¹ mannitol), the high dose of D-glucose group (HG, 30 mmol·L⁻¹ glucose), the low dose of TP group (L-TP, 30 mmol·L⁻¹ glucose plus 5 mg·L⁻¹ TP) and the high dose of TP group (H-TP, 30 mmol·L⁻¹ glucose plus 20 mg·L⁻¹ TP), which were cultured in 5% CO₂ at 37 °C, respectively. Firstly, the effects of TP on the cell morphology of HGMCs were observed after 72 h-intervention. Secondly, the cell cycle, the positive rate of senescence-associated-β-galactosidase (SA-β-gal) staining and the telomere length were detected, respectively. Finally, the protein expressions of p53, p21 and Rb in the p53-p21-Rb signaling pathway were investigated, respectively. And the expressions of p-STAT3 and miR-126 were examined severally. The results indicated that HG not only arrested the cell cycle in G₁ phase but also increased the positive rate of SA-β-gal staining, and shortened the telomere length. HG led to the protein over-expressions of p53, p21 and Rb and HGMCs senescence by activating the p53-p21-Rb signaling pathway. In addition, L-TP delayed HGMCs senescence by improving the cell cycle G₁ arrest, reducing SA-β-gal staining positive rate and lengthening the telomere length. L-TP reduced the protein over-expressions of p53, P21 and Rb induced by HG and inhibited the telomere-p53-p21-Rb signaling pathway. Moreover, the expression of p-STAT3 was increased and the expression of miR-126 was decreased in HGMCs induced by HG. L-TP reduced the expression of p-STAT3 and increased the expression of miR-126 in HGMCs. In conclusion, HG could induce HGMCs senescence by activating the telomere-p53-p21-Rb signaling pathway in vitro. L-TP could delay HGMCs senescence through regulating STAT3/miR-126 expressions and inhibiting the telomere-p53-p21-Rb signaling pathway activation. These findings could provide the effective interventions in clinic for preventing and treating renal cell senescence in diabetic kidney disease.
