Background: Injury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 () is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.
Methods: Nephron-specific knockout () and nephron-specific -overexpressing () mice were generated to dissect the role of in nephron development and maintenance.
Results: Both and mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)-associated gene expression was dysregulated in mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in mouse kidneys while it was decreased in kidneys. Furthermore, expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.
Conclusions: Our results show that is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.
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http://dx.doi.org/10.1681/ASN.2020040424 | DOI Listing |
Aging Cell
December 2024
Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, China Medical University, Shenyang, China.
Little evidence exists regarding the associations between clinical parameter-based biological aging and the incidence and outcome of chronic kidney disease (CKD). Thus, we aimed to assess the associations between biological aging, genetic risk, and the risk of CKD, as well as investigate the impact of accelerated biological aging on life expectancy. 281,363 participants free of kidney diseases from the UK Biobank were included in this prospective study.
View Article and Find Full Text PDFGenes Dis
March 2025
Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
Diabetic nephropathy is a prevalent complication of diabetes and stands as the primary contributor to end-stage renal disease. The global prevalence of diabetic nephropathy is on the rise, however, due to its intricate pathogenesis, there is currently an absence of efficacious treatments to enhance renal prognosis in affected patients. The mammalian target of rapamycin (mTOR), a serine/threonine protease, assumes a pivotal role in cellular division, survival, apoptosis delay, and angiogenesis.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Background: The effect of renal impairment in patients who receive intravenous thrombolysis for acute ischemic stroke (AIS) is unclear. We aimed to determine the associations of renal impairment and clinical outcomes and any modification of the effect of intensive versus guideline-recommended blood pressure (BP) control in the BP arm of the International Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).
Methods: We conducted a analysis of the ENCHANTED BP arm, which involved 2,196 thrombolyzed AIS patients.
ESC Heart Fail
December 2024
Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.
Aims: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR).
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
December 2024
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Background: Chronic kidney disease (CKD) is on the rise, and over 50% of patients die from cardiac causes. Patients develop heart failure due to unelucidated reno-cardiac interactions, termed type 4 cardiorenal syndrome (CRS4). The aim of this study is to establish and characterize a reliable model of CRS4 in swine with marked cardiac diastolic dysfunction.
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