Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease

Heterogeneity of lymphatic vessels during embryogenesis is critical for organ-specific lymphatic function. Little is known about lymphatics in the developing kidney, despite their established roles in pathology of the mature organ. We performed three-dimensional imaging to characterize lymphatic vessel formation in the mammalian embryonic kidney at single-cell resolution. In mouse, we visually and quantitatively assessed the development of kidney lymphatic vessels, remodeling from a ring-like anastomosis under the nascent renal pelvis, a site of VEGF-C expression, to form a patent vascular plexus. We identified a heterogenous population of lymphatic endothelial cell clusters in mouse and human embryonic kidneys. Exogenous VEGF-C expanded the lymphatic population in explanted mouse embryonic kidneys. Finally, we characterized complex kidney lymphatic abnormalities in a genetic mouse model of polycystic kidney disease. Our study provides novel insights into the development of kidney lymphatic vasculature; a system which likely has fundamental roles in renal development, physiology and disease.
Source: eLife - Category: Biomedical Science Tags: Developmental Biology Human Biology and Medicine Source Type: research

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Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition–An Outstanding Challenge Attila Fintha1, Ákos Gasparics2, László Rosivall3 and Attila Sebe3,4* 12nd Department of Pathology, Semmelweis University, Budapest, Hungary 21st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary 3Department of Pathophysiology, International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary 4Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany Back in 1995, a landmark paper was published, which shaped the fi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract In inflammatory diseases, the 5-lipoxygenase (5-LO) pathway contributes to epithelial damage and fibrosis by catalyzing the production of leukotrienes. Antagonists of the 5-LO pathway are currently approved for use in patients and are well tolerated. We found that expression of 5-LO is strongly induced in three models of chronic kidney disease, unilateral ureteral obstruction (UUO), folate nephropathy, and an orthologous mouse model of polycystic kidney disease. Immunohistochemistry showed that macrophages are the dominant source of 5-LO. Zileuton, an FDA-approved antagonist of 5-LO, significantly reduced...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
Conclusions: As surgeon comfort and experience with robotic assisted surgery grows, robotic surgery can successfully be applied to less frequently performed procedures. Here we successfully performed a robotic assisted radical cystoprostatectomy with intracorporeal ileal conduit urinary diversion for a renal transplant recipient.
Source: International Braz J Urol - Category: Urology & Nephrology Source Type: research
SummaryThe present study aimed to examine the value of ultrasonic soft markers in prenatal screening by analyzing the clinical outcome of fetuses with ultrasonic soft markers during the second trimester of pregnancy. A retrospective analysis was performed to evaluate the outcome of 591 fetuses with ultrasonic soft markers from January 2015 to August 2016 in Zhongnan Hospital of Wuhan University, China. It was found that 591 fetuses showed ultrasonic soft markers in 4927 cases with the occurrence rate being 12.0%. Among them, 564 fetuses (95.4%) were delivered and the remaining 27 cases (4.6%) were aborted. Five hundred and...
Source: Journal of Huazhong University of Science and Technology -- Medical Sciences -- - Category: Research Source Type: research
In this study, we identified for the first time that β-arrest in-1 was upregulated in the kidney from mice with unilateral ureteral obstruction nephropathy as well as in the paraffin-embedded sections of human kidneys from the patients with diabetic nephropathy, polycystic kidney, or uronephrosis, which normally causes renal fibrosis. Deficiency of β-arrestin -1 in mice significantly alleviated renal fibrosis by the regulation of inflammatory responses, kidney fibroblast activation, and epithelial-mesenchymal transition (EMT) in both in vivo and in vitro studies. Furthermore, we found that among the major isoform...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research
We report here that JQ1–induced BET inhibition modulated the in vitro expression of genes involved in several biologic processes, including inflammation and immune responses. Gene silencing of BRD4, an important BET protein, and chromatin immunoprecipitation assays showed that JQ1 alters the direct association of BRD4 with acetylated histone–packaged promoters and reduces the transcription of proinflammatory genes (IL-6, CCL-2, and CCL-5). In vivo, JQ1 abrogated experimental renal inflammation in murine models of unilateral ureteral obstruction, antimembrane basal GN, and infusion of Angiotensin II. Notably, JQ...
Source: Journal of the American Society of Nephrology : JASN - Category: Urology & Nephrology Authors: Tags: Basic Research Source Type: research
AbstractTo evaluate safety and efficacy of minipercutaneous nephrolithotomy (Mini-PNL) in management of stones in different types of renal anomalies. Patients with stones ≥2 cm or SWL-resistant stones in anomalous-kidneys treated by Mini-PNL between March 2010 and September 2012 were included prospectively. Mini-PNL was done under regional anesthesia in prone position with fluoroscopic guidance through 18 Fr sheath using semirigid ureteroscope (8.5/11.5 Fr) and pn eumatic lithotripter. All patients were followed-up for 2–3 years. Stone-free rate was defined as absence of residual fragments ≥2 mm....
Source: Urolithiasis - Category: Urology & Nephrology Source Type: research
Conclusion: Our case suggested surgery combined with adjuvant chemotherapy might be effective treatments in such a condition.
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
CONCLUSIONS: The low rate of morbidity and excellent survival rates make kidney transplant an excellent option for patients with polycystic kidney disease. Although fear of future appearance of polycystic kidney disease may reduce the rate of related living donors, our study showed that graft and patient survival rates in the living-donor group were as high as in the deceased-donor group. PMID: 26450465 [PubMed - in process]
Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantation - Category: Transplant Surgery Authors: Tags: Exp Clin Transplant Source Type: research
Conclusions VHL/PBRM1 mutations confirmed 3rd subtype identified and under review but appears to be mis-classified tumors.  Shows value of molecular methods rather than new mechanistic insights. Integration with survival outcome—suggests molecular detailing can be prognostic Full integrative analysis in process Preliminary data can be found at FoxO Transcription Factors in mTORC1- Activated Renal Tumorigenesis:  Implications for the RCC Treatment Boyi Gan, MD Anderson Cancer Center FoxO Family Transcription Factors:  mammals possess FoxO...
Source: Kidney Cancer Association - Category: Urology & Nephrology Source Type: news
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