Group 1 innate lymphoid cells protect liver transplants from ischemia-reperfusion injury via an interferon gamma-mediated pathway.

As important immune regulatory cells, whether innate lymphoid cells (ILCs) are involved in liver transplantation (LT) remains unclear. In a murine orthotopic LT model, we dissected roles of ILCs in liver ischemia-reperfusion injury (IRI). Wild-type (WT) grafts suffered significantly higher IRI in Rag2-γc double knockout (DKO) than Rag2 knockout (KO) recipients, in association with downregulation of group 1 ILCs genes, including interferon gamma.

Multilevel Intervention to Improve Racial Equity in Access to Kidney Transplant.

Background: African Americans (AAs) have reduced access to kidney transplant (KTX). Our center undertook a multilevel quality improvement endeavor to address KTX access barriers, focused on vulnerable populations. This program included dialysis center patient/staff education, embedding telehealth services across South Carolina, partnering with community providers to facilitate testing/procedures, and increased use of high-risk donors.

Connexins in endothelial cells as a therapeutic target for solid organ transplantation.

Connexins are a class of membrane proteins widely distributed throughout the body and have various functions based on their location and levels of expression. More specifically, connexin proteins expressed in endothelial cells (ECs) have unique roles in maintaining EC barrier integrity and function-a highly regulated process that is critical for pro-inflammatory and pro-coagulant reactions. In this minireview, we discuss the regulatory influence connexin proteins have in maintaining EC barrier integrity and their role in ischemia-reperfusion injury as it relates to organ transplantation.

A Dialysis Center Educational Video Intervention Increases Patient Self-Efficacy and Kidney Transplant Evaluations.

The optimal treatment for end-stage kidney disease is renal transplant. However, only 1 in 5 (21.5%) patients nationwide receiving dialysis are on a transplant waitlist.

Association of High Burden of End-stage Kidney Disease With Decreased Kidney Transplant Rates With the Updated US Kidney Allocation Policy.

Importance: The Organ Procurement and Transplantation Network (OPTN) approved changes to the US kidney allocation system in 2019. The potential effects of this policy change using transplant rates normalized to end-stage kidney disease (ESKD) incidence have not been investigated.

Objective: To estimate how the OPTN kidney allocation policy will affect areas of the US currently demonstrating low rates of kidney transplant, when accounting for the regional burden of ESKD.

Costs and factors associated with heart failure following kidney transplantation - a single-center retrospective cohort study.

The number of adults with heart failure (HF) will increase by ~50% between 2012 and 2030. Among kidney transplant recipients, HF accounts for 16% of all post-transplant admissions. We describe the burden of HF and predictors of healthcare utilization following kidney transplantation.

Hospital admissions and emergency department visits among kidney transplant recipients.

Reducing acute care utilization is a means of improving long-term patient outcomes. We sought to assess high inpatient (IP) admission and standalone emergency department (ED) utilization within a 9-month period post-kidney transplantation and to identify mutable factors to reduce utilization. In this ten-year retrospective study, 1599 adult kidney transplant recipients were identified.

An African American Perspective on Familial Notification of Becoming a Registered Organ Donor.

Introduction: Studies demonstrate that family notification is much less frequent in African Americans than in Caucasians. Familial notification of one's decision to become a registered organ donor (ROD) is important to ensure adherence to the decedent's donation decision and to disseminate prodonation attitudes. The purpose of this study was to explore the experiences of familial notification among recent African American RODs and to identify intervention strategies to overcome potential barriers to the notification process.

Development and future deployment of a 5 years allograft survival model for kidney transplantation.

Aim: Identifying kidney transplant patients at highest risk for graft loss prior to loss may allow for effective interventions to improve 5 years survival.

Methods: We performed a 10 years retrospective cohort study of adult kidney transplant recipients (n = 1747). We acquired data from electronic health records, United Network of Organ Sharing, social determinants of health, natural language processing data extraction, and real-time capture of dynamically evolving clinical data obtained within 1 year of transplant; from which we developed a 5 years graft survival model.

A quantitative appraisal of African Americans' decisions to become registered organ donors at the driver's license office.

African American (AA) organ donation registration rates fall short of national objectives. The goal of the present study was to utilize data acquired from a quantitative telephone survey to provide information for a future Department of Motorized Vehicles (DMV) intervention to increase AA organ donor registration at the DMV. AAs (n = 20 177) that had visited an Alabama DMV office within a 3-month period were recruited via direct mailing to participate in a quantitative phone survey.

Renal Function Variability: An Independent Risk Factor for Graft Loss and Death following Kidney Transplantation.

Background: Several studies have been performed to evaluate surrogate markers of long-term allograft function in renal transplant recipients. These include serum creatinine, estimated glomerular filtration rate (eGFR), slope of eGFR, and more recently eGFR variability. The aim of this study was to measure eGFR slope while assessing the variability of this slope and if high variability occurring at any time post-transplant was predictive of poorer long-term outcomes in a large cohort of kidney transplant recipients.

Frizzled-5: a high affinity receptor for secreted frizzled-related protein-2 activation of nuclear factor of activated T-cells c3 signaling to promote angiogenesis.

Secreted frizzled-related protein 2 (SFRP2) is a pro-angiogenic factor expressed in the vasculature of a wide variety of human tumors, and modulates angiogenesis via the calcineurin-dependent nuclear factor of activated T-cells cytoplasmic 3 (NFATc3) pathway in endothelial cells. However, until now, SFRP2 receptor for this pathway was unknown. In the present study, we first used amino acid alignments and molecular modeling to demonstrate that SFRP2 interaction with frizzled-5 (FZD5) is typical of Wnt/FZD family members.

Angiotensin II receptors and peritoneal dialysis-induced peritoneal fibrosis.

The vasoactive hormone angiotensin II initiates its major hemodynamic effects through interaction with AT1 receptors, a member of the class of G protein-coupled receptors. Acting through its AT1R, angiotensin II regulates blood pressure and renal salt and water balance. Recent evidence points to additional pathological influences of activation of AT1R, in particular inflammation, fibrosis and atherosclerosis.

The conformational signature of β-arrestin2 predicts its trafficking and signalling functions.

Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'.

Clathrin-dependent internalization of the angiotensin II AT₁A receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells.

The major effects of Angiotensin II (AngII) in vascular tissue are mediated by AngII AT1A receptor activation. Certain effects initiated by AT1A receptor activation require receptor internalization. In rat aortic vascular smooth muscle cells (RASMC), AngII stimulates cyclooxygenase 2 protein expression.

Stimulation of Cyclooxygenase 2 Expression in Rat Peritoneal Mesothelial Cells.

Objective: Since peritoneal dialysis causes peritoneal fibrosis, we examined how glucose (osmotic factor), mannitol (osmotic control), and angiotensin II (AngII) regulate proinflammatory cyclooxygenase 2 (COX-2) in primary rat peritoneal mesothelial cells. Materials and Methods: For this study, we used the following material (n = 4-8 cell lines): cells, passages 1-2; I-AngII receptor surface binding (AT1R antagonist losartan, AT2R antagonist PD123319; both 10 µM); intracellular calcium probe calcium-5; COX-2 immunoblotting (β-actin normalized); real-time PCR of COX-2 gene PTGS2, and NF-κB inhibitor Ro-1069920 (5 µM). Results: AngII surface receptors were predominantly AT1R (minimally AT2R).

Lack of renoprotective effect of chronic intravenous angiotensin-(1-7) or angiotensin-(2-10) in a rat model of focal segmental glomerulosclerosis.

Unopposed angiotensin (Ang) II-mediated cellular effects may lead to progressive glomerulosclerosis. While Ang-II can be locally generated in the kidneys, we previously showed that glomerular podocytes primarily convert Ang-I, the precursor of Ang-II, to Ang-(1-7) and Ang-(2-10), peptides that have been independently implicated in biological actions opposing those of Ang-II. Therefore, we hypothesized that Ang-(1-7) and Ang-(2-10) could be renoprotective in the fawn-hooded hypertensive rat, a model of focal segmental glomerulosclerosis.

The arrestin-selective angiotensin AT1 receptor agonist [Sar1,Ile4,Ile8]-AngII negatively regulates bradykinin B2 receptor signaling via AT1-B2 receptor heterodimers.

The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT1 receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B1 and B2 bradykinin receptors.

Angiotensin II activates NF-κB through AT1A receptor recruitment of β-arrestin in cultured rat vascular smooth muscle cells.

Activation of the angiotensin type 1A receptor (AT1AR) in rat aorta vascular smooth muscle cells (RASMC) results in increased synthesis of the proinflammatory enzyme cyclooxygenase-2 (COX-2). We previously showed that nuclear localization of internalized AT1AR results in activation of transcription of the gene for COX-2, i.e.

Biasing the parathyroid hormone receptor: relating in vitro ligand efficacy to in vivo biological activity.

Recent advances in our understanding of the pluridimensional nature of GPCR signaling have provided new insights into how orthosteric ligands regulate receptors, and how the phenomenon of functional selectivity or ligand "bias" might be exploited in pharmaceutical design. In contrast to the predictions of simple two-state models of GPCR function, where ligands affect all aspects of GPCR signaling proportionally, current models assume that receptors exist in multiple "active" conformations that differ in their ability to couple to different downstream effectors, and that structurally distinct ligands can bias signaling by preferentially stabilizing different active states. The type 1 parathyroid hormone receptor (PTH(1)R) offers unique insight into both the opportunities and challenges of exploiting ligand bias in pharmaceutical design, not only because numerous "biased" PTH analogs have been described but also because many of them have been characterized for biological activity in vivo.

The bradykinin B(2) receptor induces multiple cellular responses leading to the proliferation of human renal carcinoma cell lines.

Background: The vasoactive peptide bradykinin (BK) acts as a potent growth factor for normal kidney cells, but there have been few studies on the role of BK in renal cell carcinomas.

Purpose: In this study, we tested the hypothesis that BK also acts as a mitogen in kidney carcinomas, and explored the effects of BK in human renal carcinoma A498 cells.

Methods: The presence of mRNAs for BK B(1) and BK B(2) receptors in A498 cells was demonstrated by reverse transcription-polymerase chain reaction.

Enzymatic processing of angiotensin peptides by human glomerular endothelial cells.

The intraglomerular renin-angiotensin system (RAS) is linked to the pathogenesis of progressive glomerular diseases. Glomerular podocytes and mesangial cells play distinct roles in the metabolism of angiotensin (ANG) peptides. However, our understanding of the RAS enzymatic capacity of glomerular endothelial cells (GEnCs) remains incomplete.

Angiotensin II-induced cyclooxygenase 2 expression in rat aorta vascular smooth muscle cells does not require heterotrimeric G protein activation.

Angiotensin II (AngII) initiates cellular effects via its G protein-coupled angiotensin 1 (AT(1)) receptor (AT(1)R). Previously, we showed that AngII-induced expression of the prostanoid-producing enzyme cyclooxygenase 2 (COX-2) was dependent upon nuclear trafficking of activated AT(1)R. In the present study, mastoparan (an activator of G proteins), suramin (an inhibitor of G proteins), 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122; a specific inhibitor of phospholipase C), and sarcosine(1)-Ile(4)-Ile(8)-AngII (SII-AngII; a G protein-independent AT(1)R agonist) were used to determine the involvement of G proteins and AT(1A)R trafficking in AngII-stimulated COX-2 protein expression in human embryonic kidney-293 cells stably expressing AT(1A)/green fluorescent protein receptors and cultured vascular smooth muscle cells, respectively.

Essential role of c-Cbl in amphiregulin-induced recycling and signaling of the endogenous epidermal growth factor receptor.

The intracellular processing of the epidermal growth factor receptor (EGFR) induced by epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) has been studied meticulously, with the former resulting in EGFR degradation and the latter in EGFR recycling to the plasma membrane. However, little is known about how other EGF family growth factors affect the trafficking of the EGFR. Additionally, although both EGF and TGF-alpha have been shown to effectively induce initial c-Cbl (ubiquitin ligase)-mediated ubiquitination of the EGFR, limited information is available regarding the role of c-Cblin the trafficking and signaling of recycling EGFR.