Valsartan- and melatonin-supported adipose-derived mesenchymal stem cells preserve renal function in chronic kidney disease rat through upregulation of prion protein participated in promoting PI3K-Akt-mTOR signaling and cell proliferation

被引：25

作者：

Yang, Chih-Chao ^{[1
]}

Sung, Pei-Hsun ^{[1
,2
,3
,4
]}

Chen, Kuan-Hung ^{[1
,3
,5
]}

Chai, Han-Tan ^{[1
,2
]}

Chiang, John Y. ^{[6
]}

Ko, Sheung-Fat ^{[1
,7
]}

Lee, Fan-Yen ^{[1
,8
,9
]}

Yip, Hon-Kan ^{[1
,2
,3
,4
,10
,11
,12
,13
]}

机构：

[1] Chang Gung Univ, Coll Med, Kaohsiung 83301, Taiwan

[2] Kaohsiung Chang Gung Mem Hosp, Div Cardiol, Dept Internal Med, Kaohsiung 83301, Taiwan

[3] Kaohsiung Chang Gung Mem Hosp, Ctr Shockwave Med & Tissue Engn, Kaohsiung 83301, Taiwan

[4] Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed, Kaohsiung 83301, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Anesthesiol, Kaohsiung 83301, Taiwan

[6] Natl Sun Yat Sen Univ, Dept Comp Sci & Engn, Kaohsiung 80424, Taiwan

[7] Kaohsiung Chang Gung Mem Hosp, Dept Radiol, Kaohsiung 83301, Taiwan

[8] Kaohsiung Chang Gung Mem Hosp, Div Thorac & Cardiovasc Surg, Dept Surg, Kaohsiung 83301, Taiwan

[9] Tri Serv Gen Hosp, Div Cardiovasc Surg, Dept Surg, Natl Def Med Ctr, Taipei, Taiwan

[10] Chang Gung Univ, Sch Med, Coll Med, Taoyuan, Taiwan

[11] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan

[12] Asia Univ, Dept Nursing, Taichung 41354, Taiwan

[13] Xiamen Chang Gung Hosp, Div Cardiol, Dept Internal Med, Xiamen 361028, Fujian, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2022年 / 146卷

关键词：

Cellular prior protein; Adipose-derived mesenchymal stem cells; Melatonin; Valsartan; Oxidative stress; ISCHEMIA-REPERFUSION INJURY; RENIN INHIBITION; NATIONAL-HEALTH; BISPHENOL-A; THERAPY; CKD; MICROALBUMINURIA; PREVALENCE; CREATININE; BLOCKADE;

D O I：

10.1016/j.biopha.2021.112551

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

This study tested the hypothesis that valsartan (Val) and melatonin (Mel)-assisted adipose-derived mesenchymal stem cells (ADMSCs) preserved the residual renal function in chronic kidney disease (CKD) rat through promoting cellular-prior-protein (PrPC) to upregulate PI3K/Akt/mTOR signaling and cell proliferation. In vitro study demonstrated that as compared with CKD-derived-ADMSCs, Val/Mel/overexpression of PrPC-treated CKD derived-ADMSCs significantly upregulated cell proliferation and protein expressions of PrPC and phosphorylated (p)-PI3K/p-Akt/p-mTOR, and downregulated oxidative stress (all p < 0.001). Rats (n = 42) were categorized into group 1 (sham-operated-control), group 2 (CKD), group 3 (CKD + ADMSCs/1.2 x10 6 cells) + Mel/20 mg/kg/ day), group 4 (CKD + siRNA-PrPC-ADMSCs/1.2 x10 6 cells), group 5 (CKD + ADMSCs/1.2 x10 6 cells + Val/20 mg/kg/day) and group 6 (CKD + Val + Mel). By day 35, the kidney specimens were harvested and the result showed that the protein expression of PrPC was highest in group 1, lowest in groups 2/4 and significantly lower in group 6 than in groups 3/5, but it was similar in groups 3/5 (all p < 0.0001). The protein expressions of cellstress-signaling (p-PI3K/p-Akt/p-mTOR) and cell-cycle activity (cyclin-D1/clyclin-E2/Cdk2/Cdk4) exhibited an identical pattern, whereas the protein expressions of oxidative-stress (NOX-1/NOX-2)/mitochondrial fission (PINK1/DRP1)/apoptosis (cleaved-capsase3/cleaved-PARP) and fibrosis (TFG-beta/Smad3) as well as creatinine/ BUN levels, ratio of urine-protein to urine-creatine and kidney-injured score exhibited an opposite pattern of PrPC among the groups (all p < 0.0001). In conclusion, Mel/Val facilitated-ADMSCs preserved renal architecture and function in CKD rat through promoting PrPC to regulate the cell proliferation/oxidative-stress/cell-stress signalings.

引用

页数：17

共 47 条

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