Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways.
10.19540/j.cnki.cjcmm.20200709.401
- Author:
Qi-Jun FANG
1
;
Jian-Jing LIU
2
;
Yi-Gang WAN
3
;
Bu-Hui LIU
4
;
Yue TU
5
;
Wei WU
3
;
Ying-Lu LIU
3
;
Wen-Wen WANG
1
;
Mei-Zi WANG
1
;
Hong-Yun YEE
1
;
Can-Can YUAN
1
;
Fee-Lan CHONG
6
Author Information
1. Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Chinese Medicine and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210029, China.
2. Department of Nephrology, Jiangsu Province Hospital on Integration of Chinese and Western Medicine Nanjing 210028, China.
3. Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School Nanjing 210008, China.
4. Nephrology Division, Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, China.
5. Department of Traditional Chinese Medicine Health Preservation, Acupuncture and Moxibustion and Massage College·Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine Nanjing 210023, China.
6. School of Pharmacy, Management and Science University Shah Alam 40100, Malaysia.
- Publication Type:Journal Article
- Keywords:
AMPK-ULK1 signaling pathway;
aging;
autophagy;
fucoidan;
human proximal renal tubular epithelial cells
- MeSH:
Aging;
Autophagy;
Epithelial Cells;
Humans;
Polysaccharides;
Signal Transduction
- From:
China Journal of Chinese Materia Medica
2020;45(24):6003-6011
- CountryChina
- Language:Chinese
-
Abstract:
Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.
