Sitagliptin and shock wave-supported peripheral blood derived endothelial progenitor cell therapy effectively preserves residual renal function in chronic kidney disease in rat—role of dipeptidyl peptidase 4 inhibition

Pei-Hsun Sung; Kuan-Hung Chen; Yi-Chen Li; John Y. Chiang; Mel S. Lee; Hon-Kan Yip

Biomedicine & Pharmacotherapy (Mar 2019)

Sitagliptin and shock wave-supported peripheral blood derived endothelial progenitor cell therapy effectively preserves residual renal function in chronic kidney disease in rat—role of dipeptidyl peptidase 4 inhibition

Pei-Hsun Sung,
Kuan-Hung Chen,
Yi-Chen Li,
John Y. Chiang,
Mel S. Lee,
Hon-Kan Yip

Affiliations

Pei-Hsun Sung: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, ROC
Kuan-Hung Chen: Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, ROC; Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC
Yi-Chen Li: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC
John Y. Chiang: Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC;; Quanzhou University of Information Engineering, Quanzhou, China
Mel S. Lee: Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC; Corresponding author.
Hon-Kan Yip: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, ROC; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, ROC; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC; Department of Nursing, Asia University, Taichung, 41354, Taiwan, ROC; Corresponding author at: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC.

Journal volume & issue: Vol. 111
pp. 1088 – 1102

Abstract

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This study tested whether sitagliptin and shock wave (SW)-assisted circulatory-derived autologous endothelial progenitor cell (EPC) therapy would effectively preserve residual renal function in chronic kidney disease (CKD) induced by 5/6 left-nephrectomy/remove right kidney plus daily feeding high-protein diet (HPD) in rat. Adult-male SD rats (n = 40) were categorized into group 1 (sham-operated control with HPD), group 2 (HPD-CKD), group 3 [HPD-CKD + EPC (1.2 × 106 cell)/intra-vessel administration by day 14 after CKD-induction], group 4 [HPD-CKD + SW (0.12 mJ/mm2/180 shorts) at days 14/21/28 after CKD-induction by ultrasound-guided application] and group 5 [HPD-CKD + SW + EPC + sitagliptin (Sita; 600 mg/kg/day since day 14 after CKD induction)]. All animals were euthanized by day 60. By day 60, renal blood flow (RBF) was highest in group 1 and progressively increased from groups 2 to 5, whereas the levels of creatinine/BUN/proteinuria exhibited an opposite pattern of RBF among the five groups (all p < 0.001). The circulating levels of GLP-1/SDF-1α and protein levels of angiogenesis (VEGF/SDF-1α/CXCR4) and GLP-1R in kidney were progressively increased from groups 1 to 5, whereas circulating DPP4 activity exhibited an opposite pattern of SDF-1α among the groups (all p < 0.0001). The protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptosis (Bax/caspase-3/PARP), fibrosis (Smad3/TGF-ß) and inflammation (TNF-α/NF-κB/MMP-2) and kidney injury score displayed an opposite pattern, whereas the protein expressions of TMP2, endothelial-cell markers (CD31/eNOS) and podocyte integrity biomarkers (podocin/ZO-1/synaptopodin) exhibited an identical pattern of RBF among the groups (all p < 0.001). In conclusion Sita associated SW-assisted EPC effectively protected residual renal function in CKD.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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