A5040761993- Renal Diseases and Glomerulopathies
- Renal and related cancers
- Angiogenesis and VEGF in Cancer
- Apelin-related biomedical research
- Single-cell and spatial transcriptomics
- Hormonal Regulation and Hypertension
- Chronic Kidney Disease and Diabetes
- Circadian rhythm and melatonin
- Biomedical Research and Pathophysiology
- Ion Transport and Channel Regulation
- Platelet Disorders and Treatments
- RNA Interference and Gene Delivery
- Blood properties and coagulation
- Photoreceptor and optogenetics research
- Cell Adhesion Molecules Research
- Birth, Development, and Health
- Renal and Vascular Pathologies
- Tissue Engineering and Regenerative Medicine
- Renin-Angiotensin System Studies
- Digestive system and related health
- Diet and metabolism studies
- Diet, Metabolism, and Disease
- Congenital limb and hand anomalies
- Sodium Intake and Health
- Ultrasound and Cavitation Phenomena
University of Southern California
2014-2024
Southern California University for Professional Studies
2024
Broad Center
2014-2016
Keck Hospital of USC
2016
Tissue regeneration is limited in several organs including the kidney, contributing to high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses presence renal progenitor cells suggest existing remodeling capacity. This study uncovered endogenous tissue mechanisms that were activated by loss body fluid salt regulated a unique niche minority cell type called macula densa (MD). Here we identified neuronal differentiation features MD sense local...
The vasoconstrictor effects of angiotensin II via type 1 receptors in vascular smooth muscle cells are well established, but the direct on endothelial (VECs) vivo and mechanisms how VECs may mitigate II-mediated vasoconstriction not fully understood. present study aimed to explore molecular pathophysiological relevance actions kidney brain microvessels vivo.
Endothelial cells are important in the maintenance of healthy blood vessels and development vascular diseases. However, origin dynamics endothelial precursors remodeling at single-cell level have been difficult to study vivo owing technical limitations. Therefore, we aimed develop a direct visual approach track fate function single over several days weeks same bed using multiphoton microscopy (MPM) transgenic Cdh5-Confetti mice kidney glomerulus as model. Individual lineage were identified...
ABSTRACT The clinical need for methods to repair and regenerate large cartilage bone lesions persists. One way make new headway is study skeletal regeneration when it occurs naturally. Cartilage typically slow incomplete. However, an exception this observation can be found in the costal cartilages, where complete has been reported humans but cellular molecular mechanisms have not yet characterized. In study, we establish a novel animal model using mouse rib cartilage. We then use test...
Podocyte calcium (Ca2+) signaling plays important roles in the (patho)physiology of glomerular filtration barrier. Overactivation podocyte transient receptor potential canonical (TRPC) channels including TRPC6 and purinergic via P2 receptors that are known mechanosensors can increase intracellular Ca2+ levels ([Ca2+]i) cause cell injury, proteinuria disease diabetes. However, mechanistic details trigger activation these pathways vivo intact environment lacking. Here we show direct visual...
Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, filtration barrier (GFB) damage, and progressive chronic kidney disease. While the basis of AS well known, molecular cellular mechanistic details disease pathogenesis have been elusive, hindering development mechanism-based therapies. Here, we performed intravital multiphoton imaging local tissue microenvironment X-linked mouse model directly visualize major...
Dual endothelin-1 (ET-1) and angiotensin II (AngII) receptor antagonism with sparsentan has strong antiproteinuric actions via multiple potential mechanisms that are more pronounced, or additive, compared current standard of care using blockers (ARBs). Considering the many ET-1 AngII on cell types, this study aimed to determine glomeruloprotective ARB losartan by direct visualization its effects in intact kidney focal segmental glomerulosclerosis (FSGS) intravital multiphoton microscopy. In...
This study discovered the high rate of protein synthesis in macula densa (MD) cells by applying direct imaging techniques with single cell resolution. Physiological activation and mammalian target rapamycin signaling played important regulatory roles this process. new feature is a novel component tubuloglomerular cross talk glomerular hemodynamic functions MD cells. Future work needed to elucidate nature (patho)physiological role specific proteins synthesized
Vascular cognitive impairment (VCI) is a growing health problem in many developed countries due to aging of its population. Aging-induced neurovascular coupling (NVC) responses and brain microvascular rarefaction have been implicated as major driving mechanisms age-related decline. One the cellular hallmarks NVC involve release vasodilator nitric oxide (NO) by endothelial cells response mediators released from activated neurons. Recent studies our group identified characterized novel,...
The control of whole-body energy metabolism involves intricate crosstalk between multiple organ systems including the gut and brain that play well-recognized roles in this process. However, important contributions mechanisms by other organs are poorly understood. Errors metabolic regulation can lead to human diseases diabetes obesity affect 75% population significant comorbidities. Improving our mechanistic understanding multi-organ health disease is essential for developing highly effcient...
Macula densa (MD) cells are major regulators of nephron, kidney, and whole body functions, including the control renal blood flow, glomerular filtration rate (GFR), renin release thus maintenance fluid electrolyte balance. Our recent studies identified high MD protein synthesis regulated by mTORC1 complex mechanistic target rapamycin (mTOR) as a novel component cell hemodynamic regulatory functions. Raptor is an essential player in mTORC1’s key roles to regulate energy homeostasis, growth,...
The role of the cell surface layer, glycocalyx is emerging in various areas biology including signaling, metabolism, and immune response. Although a decrease podocyte depth glomerular pathologies has been reported before, specific specialized between foot processes basement membrane (GBM) function dysfunction filtration barrier (GFB) elusive. Here we aimed to develop or endothelial targeting strategies gain mechanistic understanding roles GFB development albumin leakage. Our overall...
Macula densa (MD) cells, the tubular component of juxtaglomerular apparatus (JGA) are generally considered as sensor cells detecting salt (NaCl) concentration and based on this information provide feedback control glomerular hemodynamics (tubuloglomerular feedback, TGF). However, neuron-like differentiation activity non-traditional MD functions emerging. This study addressed paradigm-shifting hypothesis that rather than being simply sensory arm TGF, function nephron’s autonomous pacemaker...
The dense network of sympathetic efferent and sensory afferent nerves innervating the kidney is well recognized, however elements functional importance neurotrophin signaling in renal tissues are much less known. Peripherally innervated known to produce release nerve growth factor (NGF) which belongs family neuronal proteins essential for survival peripheral nerves. This study aimed characterize expression role NGF kidney. We hypothesized that produced by multiple tubular vascular cell types...
Cognitive impairment and dementia are major global health problems of the aging human population. It is estimated that about 55 million people were living with in 2019 this number expected to triple by 2050. Dementia can result from abnormal structure function brain blood vessels may develop a variety conditions including chronic kidney disease (CKD). Recent studies our laboratory suggest addition controlling volume pressure (renin), cell count (erythropoietin), produces novel systemic...
Introduction & Objective: Recent therapeutic advances in diabetic nephropathy (DN) including GLP-1 analogs are promising, however more efficient treatments needed with improved mechanistic understanding of their mode action. Glucagon (GCG), and GIP receptors (R) expressed the kidney. Macula densa (MD) cells play central roles controlling renal hemodynamics tissue remodeling. This study aimed to examine renoprotective effects GCG w/without incretin analogs. Methods: Intravital multiphoton...
Abstract Vascular endothelial cells (ECs) perform key pleiotropic functions to maintain body homeostasis via the regulation of organ blood flow, vascular permeability, tissue growth and inflammation, angiogenesis. Recent transcriptomic studies uncovered many EC subtypes across organs; however their specific are incompletely understood. Here we identified characterized a novel, minority subtype scattered ECs with well-defined arteriovenous zonal localization exclusively in small resistance...
Abstract Background and Aims Preliminary preclinical emerging clinical evidence indicates strong antiproteinuric actions of dual endothelin type A (ETA) angiotensin II 1 (AT1) receptor antagonism with sparsentan. These nephroprotective effects have been more pronounced in different experimental settings compared to current standard care using an AT1 blocker (ARB). Considering the broad spectrum renal (ET) (Ang II), inhibition both pathways sparsentan is postulated target multiple cell types...
SUMMARY Interoceptive neurons that sense and regulate our internal milieu have been identified in several organs except the kidney cortex despite its major importance maintaining body homeostasis. Here we report chief cell type of macula densa (MD) forms coordinated neural networks each nephron resemble peripheral ganglia. A combined vivo single-cell 4D physiology (sc4DP) scRNA sequencing approach MD mechanisms neuronal differentiation, heterogeneity (pacemaker cells), sensing local systemic...
Shroff, Urvi Nikhil; Gyarmati, Georgina; Riquier-brison, Anne; Izuhara, Audrey; Peti-Peterdi, Janos Author Information