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Role of (Pro)Renin Receptor in Cyclosporin A-Induced Nephropathy
Am J Physiol Renal Physiol. 2022 Jan 24. doi: 10.1152/ajprenal.00332.2021. Online ahead of print.ABSTRACTCalcineurin inhibitors (CNIs) such as cyclosporin A (CsA) have been widely used to improve graft survival following solid-organ transplantation. However, the clinical use of CsA is often limited by its nephrotoxicity. The present study tested the hypothesis that activation of (pro)renin receptor (PRR) contributes to CsA-induced nephropathy by activating the renin-angiotensin system (RAS). Renal injury in male Sprague-Dawley rats was induced by a low-salt diet combined with CsA as evidenced by elevated plasma creatinine ...
Source: Am J Physiol Renal P... - January 24, 2022 Category: Urology & Nephrology Authors: Jiajia Hu Yandan Tan Yanting Chen Shiqi Mo Brittin Hekking Jiahui Su Min Pu Aihua Lu J David Symons Tianxin Yang Source Type: research

Viruses, Vol. 13, Pages 1353: Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection
omas D. Friedrich The human BK polyomavirus (BKPyV) is latent in the kidneys of most adults, but can be reactivated in immunosuppressed states, such as following renal transplantation. If left unchecked, BK polyomavirus nephropathy (PyVAN) and possible graft loss may result from viral destruction of tubular epithelial cells and interstitial fibrosis. When coupled with regular post-transplant screening, immunosuppression reduction has been effective in limiting BKPyV viremia and the development of PyVAN. Antiviral drugs that are safe and effective in combating BKPyV have not been identified but would be a benefit in com...
Source: Viruses - July 13, 2021 Category: Virology Authors: Lydia E. Hainley Martina S. Hughson Amithi Narendran Ralph Smith Justin Arthur Alida Hayner-Buchan David J. Conti John M. Lehman Thomas D. Friedrich Tags: Article Source Type: research

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials
Donor organ shortage still remains a serious obstacle for the access of wait-list patients to kidney transplantation, the best treatment for End-Stage Kidney Disease (ESKD). To expand the number of transplants, the use of lower quality organs from older ECD or DCD donors has become an established routine but at the price of increased incidence of Primary Non-Function, Delay Graft Function and lower-long term graft survival. In the last years, several improvements have been made in the field of renal transplantation from surgical procedure to preservation strategies. To improve renal outcomes, research has focused on develo...
Source: Frontiers in Immunology - July 6, 2021 Category: Allergy & Immunology Source Type: research

Ischemia-Reperfusion Injury Reduces Kidney Folate Transporter Expression and Plasma Folate Levels
In conclusion, ischemia-reperfusion injury can downregulate Sp1 mediated-folate transporter expression in tubular cells, which may reduce folate reabsorption and lead to low folate status.
Source: Frontiers in Immunology - June 4, 2021 Category: Allergy & Immunology Source Type: research

Review of Current Machine Perfusion Therapeutics for Organ Preservation
Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1–8°C) and normothermic settings. Here, we...
Source: Transplantation - August 26, 2020 Category: Transplant Surgery Tags: Reviews Source Type: research

Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis
Conclusion: Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy.
Source: Theranostics - July 3, 2020 Category: Molecular Biology Authors: Ze Bo Hu, Jian Lu, Pei Pei Chen, Chen Chen Lu, Jia Xiu Zhang, Xue Qi Li, Ben Yin Yuan, Si Jia Huang, Xiong Zhong Ruan, Bi Cheng Liu, Kun Ling Ma Tags: Research Paper Source Type: research

The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria
We describe the phenotype of the Prodh2 knock out mouse model and show that the lack of HYPDH in PH mouse models results in lower levels of urinary oxalate excretion, consistent with our previous metabolic tracer and siRNA-based knockdown studies. The double knockout mouse, Grhpr KO (PH2 model) and Prodh2 KO, prevented calcium-oxalate crystal deposition in the kidney, when placed on a 1% Hyp diet. These observations support the use of the Grhpr KO mice to screen HYPDH inhibitors in vivo. Altogether these data support HYPDH as an attractive therapeutic target for PH2 and PH3 patients.Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

NF κB and Kidney Injury
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

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