Oncotarget

Research Papers:

DPP-4 enzyme deficiency protects kidney from acute ischemia-reperfusion injury: role for remote intermittent bowel ischemia-reperfusion preconditioning

Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S. Lee and Hon-Kan Yip _

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Oncotarget. 2017; 8:54821-54837. https://doi.org/10.18632/oncotarget.18962

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Abstract

Yen-Ta Chen1,*, Christopher Glenn Wallace2,*, Chih-Chao Yang3, Chih-Hung Chen4, Kuan-Hung Chen5, Pei-Hsun Sung6, Yung-Lung Chen6, Han-Tan Chai6, Sheng-Ying Chung6, Sarah Chua6, Fan-Yen Lee7, Sheung-Fat Ko8, Mel S. Lee9 and Hon-Kan Yip6,10,11,12,13

1Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Department of Plastic Surgery, Royal Devon and Exeter Hospital, Exeter, United Kingdom

3Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

4Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

5Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

6Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

7Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

8Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

9Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

10Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

11Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

12Department of Nursing, Asia University, Taichung, Taiwan

13Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

*These authors contributed equally to this work

Correspondence to:

Hon-Kan Yip, email: [email protected]

Keywords: acute kidney ischemia-reperfusion injury, preconditioning, inflammation, oxidative stress, dipeptidyl peptidase 4 deficiency

Received: January 27, 2017     Accepted: June 17, 2017     Published: July 04, 2017

ABSTRACT

We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR. Conversely, the circulating glucagon-like peptide 1 (GLP-1) levels were higher in BIR-KIR-F344 and KIR-DPP4D than KIR-F344 rats after acute KIR. KIR-F344 rats showed greater inflammation, oxidative stress, apoptosis, DNA damage and kidney injury than other rat groups. Damage to the kidney architecture in KIR-F344 rats was greater than in BIR-KIR-F344 or KIR-DPP4D rats. Expression of antioxidant proteins and GLP-1 receptor was higher in kidneys from KIR-DPP4D and BIR-KIR-F344 than KIR-F344 rats, which suggests better intrinsic responses. We therefore suggest that elevated circulating GLP-1 levels due to DPP4 deficiency and BIR preconditioning protect kidney function and architecture during acute IR injury.


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