scholarly journals RBP-J in FOXD1+ renal stromal progenitors is crucial for the proper development and assembly of the kidney vasculature and glomerular mesangial cells

2014 ◽  
Vol 306 (2) ◽  
pp. F249-F258 ◽  
Author(s):  
E. E. Lin ◽  
M. L. S. Sequeira-Lopez ◽  
R. A. Gomez
Keyword(s):  
Stromal Cells ◽  
Mesangial Cells ◽  
Complete Loss ◽  
Interior Structure ◽  
Glomerular Mesangial Cells ◽  
Renal Vasculature ◽  
Immunoglobulin Kappa ◽  
Mural Cells ◽  
Forkhead Box ◽  
Kidney Malformations

The mechanisms underlying the establishment, development, and maintenance of the renal vasculature are poorly understood. Here, we propose that the transcription factor “recombination signal binding protein for immunoglobulin kappa J region” (RBP-J) plays a key role in the differentiation of the mural cells of the kidney arteries and arterioles, as well as the mesangial cells of the glomerulus. Deletion of RBP-J in renal stromal cells of the forkhead box D1 (FOXD1) lineage, which differentiate into all the mural cells of the kidney arterioles along with mesangial cells and pericytes, resulted in significant kidney abnormalities and mortality by day 30 postpartum ( P30). In newborn mutant animals, we observed a decrease in the total number of arteries and arterioles, along with thinner vessel walls, and depletion of renin cells. Glomeruli displayed striking abnormalities, including a failure of FOXD1-descendent cells to populate the glomerulus, an absence of mesangial cells, and in some cases complete loss of glomerular interior structure and the development of aneurysms. By P30, the kidney malformations were accentuated by extensive secondary fibrosis and glomerulosclerosis. We conclude that RBP-J is essential for proper formation and maintenance of the kidney vasculature and glomeruli.

Abstract 256: Rbp-j Controls the Fate of the Kidney Vasculature

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Eugene Lin ◽  
Maria Luisa S Sequeira Lopez ◽  
Roberto A Gomez
Keyword(s):  
Stromal Cells ◽  
Mesangial Cells ◽  
Notch Signaling Pathway ◽  
Renal Vasculature ◽  
Arterial Tree ◽  
Mural Cells ◽  
Vascular Markers ◽  
Renal Abnormalities ◽  
Glomerular Tuft

Proper assembly of the renal vasculature is essential for post-natal life, and alterations to the renal vasculature are at the root of many types of cardiovascular disease. However, the mechanisms underlying the establishment, assembly and maintenance of the renal blood vessels are poorly understood. We have identified a population of renal stromal cells (marked by their expression of the transcription factor Foxd1) that differentiate to form the mural cells of the kidney arterial tree (excluding endothelial cells) and the glomerular mesangium. We previously demonstrated that RBP-J, the final transcriptional effector of the Notch signaling pathway, controls the phenotype of renin cells which are also derived from the Foxd1 lineage. We therefore hypothesized that RBP-J regulates the differentiation of stromal cells into the mural cells of the kidney arterioles. To answer this question, we deleted RBP-J in the metanephric stromal precursor cells, and found that mutant mice displayed striking kidney abnormalities in early life. Staining for vascular markers showed a significant decrease in the number of arteries and arterioles. Vessel walls were thinner due to a decrease in both the size and number of smooth muscle cells. We also noted a near absence of renin cells, supporting our earlier findings regarding the key role of RBP-J in establishing the differentiated renin cell endowment. These findings were accompanied by delayed nephrogenesis and other renal abnormalities including tubular dilation. In addition, mutant kidneys lacked Foxd1-lineage cells within the glomeruli, resulting in a depletion of mesangial cells and glomerular aneurysms. Thus, we conclude that RBP-J in Foxd1+ stromal cells plays a key role in the development of the kidney vasculature, and regulates the fate of cells that compose the arterial tree and the glomerular tuft.

scholarly journals Knockdown of FOXO6 inhibits cell proliferation and ECM accumulation in glomerular mesangial cells cultured under high glucose condition

RSC Advances ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 1741-1746 ◽  
Author(s):  
Yunqian Wang ◽  
Lei Xue ◽  
Huicong Li ◽  
Jun Shi ◽  
Baoping Chen
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Forkhead Box ◽  
High Glucose Condition ◽  
Glucose Condition ◽  
Cells Cultured

Forkhead box O 6 (FOXO6), a FOX transcription factor, has been found to be involved in diabetes mellitus and related complications.

Abstract 23: Foxd1+ Stromal Cells, the Required Progenitors for Kidney Vascular Development

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Eugene E Lin ◽  
Roberto A Gomez ◽  
Maria-Luisa S Sequeira-Lopez
Keyword(s):  
Stromal Cells ◽  
Mesangial Cells ◽  
Cell Types ◽  
Lineage Tracing ◽  
Arterial Tree ◽  
Mural Cell ◽  
Mural Cells ◽  
Selective Ablation ◽  
Similar Phenotype

The mechanisms underlying the establishment, assembly and maintenance of the renal blood vessels are poorly understood. We have previously suggested using detailed lineage tracing that renal stromal cells, characterized by their early and transient expression of the transcription factor Foxd1 , give rise to the entirety of the mural cell layer of the renal arterial tree and mesangial cells. Mural cells as defined here exclude endothelial cells, which we identified as having a separate precursor, the renal hemangioblast. To define whether Foxd1 cells are the required essential progenitor or whether their role as such could be assumed by other cell types, we used the cre-lox system to generate mice expressing diphtheria toxin subunit A in Foxd1+ cells ( Foxd1-DTA mice ) which resulted in animals with selective ablation of Foxd1+ cells. Kidneys from Foxd1-DTA embryos had a significantly reduced complement of arterial mural cells, lacking smooth muscle cells, perivascular fibroblasts, renin cells and mesangial cells. Interestingly, the few vessels that remained were also abnormal: they originated underneath the kidney capsule and elongated towards the center of the kidney rather than radiating outward from the center of the kidney. In addition, ablation of Foxd1 cells resulted in significantly delayed nephrogenesis and reduction in glomerular number. In conjunction with our previous data showing a similar phenotype upon global deletion of the Foxd1 ,gene, this illustrates the central role of Foxd1 and the cells that express it during early development. We conclude that Foxd1 stromal cells are the required progenitors for the establishment of the mural cells of the kidney arterioles and (via Foxd1 expression) for the proper origin and orientation of the kidney vessels.

Angiotensin AT1 receptor-associated protein Arap1 in the kidney vasculature is suppressed by angiotensin II

2012 ◽  
Vol 302 (10) ◽  
pp. F1313-F1324 ◽  
Author(s):  
Elisabeth Doblinger ◽  
Klaus Höcherl ◽  
Katharina Mederle ◽  
Veronika Kattler ◽  
Steen Walter ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Water Restriction ◽  
Renal Vasculature ◽  
Contralateral Kidney

Arap1 is a protein that interacts with angiotensin II type 1 (AT1) receptors and facilitates increased AT1 receptor surface expression in vitro. In the present study, we assessed the tissue localization and regulation of Arap1 in vivo. Arap1 was found in various mouse organs, with the highest expression in the heart, kidney, aorta, and adrenal gland. Renal Arap1 protein was restricted to the vasculature and to glomerular mesangial cells and was absent from tubular epithelia. A similar localization was found in human kidneys. To test the hypothesis that angiotensin II may control renal Arap1 expression, mice were subjected to various conditions to alter the activity of the renin-angiotensin system. A high-salt diet (4% NaCl, 7 days) upregulated Arap1 expression in mice by 47% compared with controls (0.6% NaCl, P = 0.03). Renal artery stenosis (7 days) or water restriction (48 h) suppressed Arap1 levels compared with controls (−64 and −62% in the clipped and contralateral kidney, respectively; and −50% after water restriction, P < 0.01). Angiotensin II infusion (2 μg·kg−1·min−1, 7 days) reduced Arap1 mRNA levels compared with vehicle by 29% ( P < 0.01), whereas AT1 antagonism (losartan, 30 mg·kg−1·day−1, 7 days) enhanced Arap1 mRNA expression by 52% ( P < 0.01); changes in mRNA were paralleled by Arap1 protein abundance. Experiments with hydralazine and epithelial nitric oxide synthase−/− mice further suggested that Arap1 expression changed in parallel with angiotensin II, rather than with blood pressure per se. Similar to in vivo, Arap1 mRNA and protein were suppressed by angiotensin II in a time- and dose-dependent manner in cultured mesangial cells. In summary, Arap1 is highly expressed in the renal vasculature, and its expression is suppressed by angiotensin II. Thus Arap1 may serve as a local modulator of vascular AT1 receptor function in vivo.

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

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