Preactivated and disaggregated shape-changed platelets protect kidney against from ischemia-reperfusion injury in rat through attenuating inflammation reaction
Yen-Ta Chen
Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorChih-Chao Yang
Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorKun-Chen Lin
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorKuan-Hung Chen
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorPei-Hsun Sung
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorPei-Lin Shao
Department of Nursing, Asia University, Taichung, Taiwan
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
Search for more papers by this authorYi-Chen Li
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorJohn Y. Chiang
Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Hon-Kan Yip
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Department of Nursing, Asia University, Taichung, Taiwan
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Correspondence
Hon-Kan Yip, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Email: [email protected]
Search for more papers by this authorYen-Ta Chen
Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorChih-Chao Yang
Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorKun-Chen Lin
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorKuan-Hung Chen
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorPei-Hsun Sung
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorPei-Lin Shao
Department of Nursing, Asia University, Taichung, Taiwan
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
Search for more papers by this authorYi-Chen Li
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorJohn Y. Chiang
Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Hon-Kan Yip
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Department of Nursing, Asia University, Taichung, Taiwan
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Correspondence
Hon-Kan Yip, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Email: [email protected]
Search for more papers by this authorAbstract
This study tested the hypothesis that preactivated and disaggregated shape-changed platelet (PreD-SCP) therapy significantly protected rat kidney from ischemia-reperfusion (IR) injury. Adult-male Sprague–Dawley rats (n = 24) were equally categorized into Groups 1 (sham-operated control [SC]), 2 (SC + PreD-SCP), 3 (IR only), and 4 (IR + PreD-SCP). By 72 hr after IR procedure, the circulatory levels of creatinine, blood urine nitrogen and inflammatory biomarkers (interleukin [IL]-6/tumor necrosis factor [TNF]-α), and ratio of urine protein to urine creatinine were significantly higher in Group 3 than in other groups and significantly higher in Group 4 than in Groups 1 and 2, but they showed no different between Groups 1 and 2 (all p < .001). The microscopic findings showed that the expressions of kidney injury score, cellular inflammation (MMP-9/CD14//F4/80), and fibrotic area were identical to the circulatory inflammation, whereas the integrity of podocyte components (ZO-1/synaptopodin/podocin) exhibited an opposite to circulatory inflammation among the four groups (all p < .0001). The protein expressions of inflammatory (TNF-α/IL-1ß/NF-κB/iNOS/TRAF6/MyD88/TLR-4), apoptotic/cell death (mitochondrial Bax/cleaved caspase-3/p-53), oxidized protein, mitogen-activated protein kinase family (p-38/p-JNK/p-c-JUN), and mitochondrial-damaged biomarkers displayed a similar pattern, whereas the antiapoptotic (Bcl-2/Bcl-XL) and integrity of mitochondrial biomarkers followed an opposite trend to circulatory inflammation among the four groups (all p < .001). PreD-SCP therapy effectively protected the kidney against IR injury.
CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest.
Supporting Information
| Filename | Description |
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| TERM_2960-Supp_0001.jpgJPEG image, 1.5 MB |
Figure S1. Immunofluorescent (IF) microscopic findings for identification of Pre Treg+ cells recruited in IR kidney. A to D) Illustrating the IF microscopic finding (800x) for identification of PreD-SCP and Treg+ cells in sham control (SC) kidney + PreD-SCP. Rale PreD-SCP or Treg+ cell was identified in the kidney. E to H) Illustrating the IF microscopic finding (800x) for identification of PreD-SCP and Treg+ cells in the left IR kidney + PreD-SCP animals. Abundant PreD-SCP (red arrows) and Treg+ cells (white arrows) were identified in the IR zone. White arrows from (E) to (H) indicated colocalized findings of CD4 and Foxp3 staining. I to L) Illustrating the IF microscopic finding (800x) for identification of PreD-SCP and Treg+ cell in the right non-IR kidney (i.e., NIR) + PreD-SCP animals. Seldom PreD-SCP or Treg+ cell was identified in the kidney parenchyma. CD4+ showed red color; FOXP3+ indicated green color, platelet was as green color and DAPI represented as nuclei. n = 2 in each group of animals. Scale bar represented in right corner =20 μm. NIR = non ischemia-reperfusion. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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