Macula densa NOS1 and transplanted renal graft function

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Lei  Wang
Organization: UNIVERSITY OF SOUTH FLORIDA
Fiscal Year: 2024
Award: $315,744
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases

Kidney transplantation is a life-saving procedure for patients with end-stage kidney
disease. Although the short-term organ survival post-transplantation has improved dramatically
over the past decades, the long-term outcomes remain unsatisfied with the survival half-lives for
transplanted renal grafts still about 10 years. In addition, organ shortage is a global crisis which
has stimulated new approaches on expansion of the donor pool by using marginal organs.
However, the employment of marginal organs has a significantly higher incidence of delayed graft
function and lower graft survival rate compared with standard criteria donors. Therefore, there is
an urgent need for new strategies to improve the long-term graft outcomes.
 In this proposal, a novel hypothesis that rescue macula densa NOS1 expression by
renal alkalization with bicarbonate improves transplanted graft outcomes will be tested.
 The findings of the present proposal will provide a novel strategy with potential
translational significance that could be applied to either donors or recipients during kidney
transplantation. Additionally, the underlying mechanisms and potential targets will be examined.
Renal alkalization to enhance the expression of macula densa NOS1 expression in donors or
recipients is anticipated to be a simple and effective method that is used in the expansion of the
donor pool and improvement of long-term graft survival.

Terms: <BNOS><Bicarbonates><Cardiac Death><Conscious><Consciousness><Data><Deterioration><EDRF Synthase><ESRD><Employment><End stage renal failure><End-Stage Kidney Disease><End-Stage Renal Disease><Endothelium-Derived Growth Factor Synthase><Exhibits><Feedback><Generations><Glomerular Filtration Rate><Graft Survival><Grafting Procedure><Guanylyl Cyclase-Activating Factor Synthase><HCO3><Half-Life><Hydrogen Carbonates><In Vitro><Incidence><Injury to Kidney><Intake><Ischemia><Ischemia-Reperfusion Injury><Kidney><Kidney Grafting><Kidney Transplantation><Kidney Transplants><Kidney Urinary System><Life><Macula densa><Measurement><Measures><Mediating><Methods><Mice><Mice Mammals><Murine><Mus><NC-NOS><NNOS><NO Synthase><NOS 1 protein><NOS type I><NOS1><NOS1 gene><NOS1 protein><Nerve Cells><Nerve Unit><Neural Cell><Neural Constitutive Nitric Oxide Synthase><Neurocyte><Neurons><Nitric Oxide Synthase><Nitric Oxide Synthase Type I><Nitric-Oxide Synthetase><Organ><Organ Donor><Organ Survival><Organ Transplantation><Organ Transplants><Outcome><Patients><Play><Preventative strategy><Prevention><Prevention strategy><Preventive strategy><Procedures><RNA Splicing><Renal Grafting><Renal Transplantation><Renal Transplants><Renal function><Reperfusion Damage><Reperfusion Injury><Risk Factors><Role><Splicing><Survival Rate><Testing><Transplantation><Variant><Variation><Wild Type Mouse><brain nitric oxide synthase><delayed graft function><experience><experiment><experimental research><experimental study><experiments><graft function><hemodynamics><improved><in vitro activity><in vivo><kidney function><kidney injury><kidney tx><nNOS enzyme><neuronal><neuronal NOS><neuronal form of nitric oxide synthase><neuronal nitric oxide synthase><new approaches><nitric oxide synthase 1><novel><novel approaches><novel strategies><novel strategy><organ allograft><organ graft><organ xenograft><post-transplant><post-transplantation><posttransplant><posttransplantation><protein purification><renal><renal injury><response><social role><therapeutic target><translational opportunities><translational potential><transplant><wildtype mouse>