Track topics on Twitter Track topics that are important to you
In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced production of fibroblast-derived erythropoietin, a hormone that stimulates erythropoiesis. Despite their importance in chronic kidney disease, the origin and regulatory mechanism of fibroblasts remain unclear. Here, we have demonstrated that the majority of erythropoietin-producing fibroblasts in the healthy kidney originate from myelin protein zero-Cre (P0-Cre) lineage-labeled extrarenal cells, which enter the embryonic kidney at E13.5. In the diseased kidney, P0-Cre lineage-labeled fibroblasts, but not fibroblasts derived from injured tubular epithelial cells through epithelial-mesenchymal transition, transdifferentiated into myofibroblasts and predominantly contributed to fibrosis, with concomitant loss of erythropoietin production. We further demonstrated that attenuated erythropoietin production in transdifferentiated myofibroblasts was restored by the administration of neuroprotective agents, such as dexamethasone and neurotrophins. Moreover, the in vivo administration of tamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well as fibrosis in a mouse model of kidney fibrosis. These findings reveal the pathophysiological roles of P0-Cre lineage-labeled fibroblasts in the kidney and clarify the link between renal fibrosis and renal anemia.
This article was published in the following journal.
Name: The Journal of clinical investigation
There is emerging evidence that tubulointerstitial fibrosis is the final common pathway of the majority of chronic progressive renal diseases, including diabetic nephropathy (DN). Zinc, an essential d...
Renal fibrosis is a common complication of diabetic nephropathy and is a major cause of end-stage renal disease. Despite the suggested link between renal fibrosis and microRNA (miRNA) dysregulation in...
Epithelial-mesenchymal transition (EMT) plays a critical role in renal fibrosis. We hypothesize that mitochondrial DNA damage and DNA deletions caused by reactive oxygen species (ROS) during renal isc...
Renal fibrosis is a hallmark feature of chronic kidney disease, which is reflected by proliferation and migration of interstitial fibroblasts and extracellular matrix (ECM) accumulation. β-Aminoisobu...
The excessive accumulation of extracellular matrix (ECM) in the renal tubulointerstitium is a key component of chronic renal damage in lupus nephritis (LN) and a critical determinant of the disease pr...
The goal of this study is to evaluate the role of nutritional Vitamin D deficiency as a potential contributor to the morbidity witnessed in patients with end-stage renal disease
This is a Phase I, open-label study evaluating the PK of S-1 components and their metabolites in patients with advanced solid tumors and varying degrees of renal function. Patients will be...
Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients
Recently, early biomarkers of renal interstitial fibrosis have been identified, amongst them de novo expression of vimentin by tubular epithelial cells, which is an intermediate filament, ...
The objective of this study is to prospectively monitor the incidence of adverse drug reactions, specifically NSF during routine use of gadoversetamide in a large number of patients with m...
- exercise capacities are still altered after heart transplantation partly due to peripheral endothelial dysfunction - cyclosporin-induced renal dysfunction may be due to renal e...
The amount of PLASMA that perfuses the KIDNEYS per unit time, approximately 10% greater than effective renal plasma flow (RENAL PLASMA FLOW, EFFECTIVE). It should be differentiated from the RENAL BLOOD FLOW; (RBF), which refers to the total volume of BLOOD flowing through the renal vasculature, while the renal plasma flow refers to the rate of plasma flow (RPF).
Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN.
Condition where a primary dysfunction of either heart or kidney results in failure of the other organ (e.g., HEART FAILURE with worsening RENAL INSUFFICIENCY).
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE. The most severe form is KIDNEY FAILURE. Renal function may deteriorate slowly (RENAL INSUFFICIENCY, CHRONIC) or precipitously (RENAL INSUFFICIENCY, ACUTE).
Distention of KIDNEY with the presence of PUS and suppurative destruction of the renal parenchyma. It is often associated with renal obstruction and can lead to total or nearly total loss of renal function.
Benign Prostatic Hyperplasia (BPH) Erectile Dysfunction Urology Urology is the branch of medicine concerned with the urinary tract and diseases that affect it. Examples include urethritis, urethrostenosis and incontinence. Urology is a su...
Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experi...
Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...