Vascular Growth Factors and Glomerular Disease

Bartlett, Christina S.; Jeansson, Marie; Quaggin, Susan E.

doi:10.1146/annurev-physiol-021115-105412

Cited by 93 publications

(87 citation statements)

References 150 publications

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“…Foot processes use an integrin-based protein complex to attach and deliver key components to the underlying glomerular basement membrane (GBM) and thereby to communicate with endothelial and mesangial cells [38, 39]. Maintaining these critical foot process inter-relationships under hypertrophying conditions, particularly when rapidly occurring over short periods of time, must impose remarkable logistical challenges in space and time that have to be accommodated by as yet poorly understood signaling mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Podocyte number and density changes during early human life

et al. 2016

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BackgroundPodocyte depletion, which drives progressive glomerulosclerosis in glomerular diseases, is caused by a reduction in podocyte number, size or function in the context of increasing glomerular volume.MethodsKidneys obtained at autopsy from premature and mature infants who died in the first year of life (n = 24) were used to measure podometric parameters for comparison with previously reported data from older kidneys.ResultsGlomerular volume increased 4.6-fold from 0.13 ± 0.07 μm3 x106 in the pre-capillary loop stage, through 0.35 μm3 x106 at the capillary loop, to 0.60 μm3 x106 at the mature glomerular stage. Podocyte number per glomerulus increased from 326 ± 154 per glomerulus at the pre-capillary loop stage to 584 ± 131 per glomerulus at the capillary loop stage of glomerular development to reach a value of 589 ± 166 per glomerulus in mature glomeruli. Thus, the major podocyte number increase occurs in the early stages of glomerular development, in contradistinction to glomerular volume increase, which continues after birth in association with body growth.ConclusionsAs glomeruli continue to enlarge, podocyte density (number per volume) rapidly decreases, requiring a parallel rapid increase in podocyte size that allows podocyte foot processes to maintain complete coverage of the filtration surface area. Hypertrophic stresses on the glomerulus and podocyte during development and early rapid growth periods of life are therefore likely to play significant roles in determining how and when defects in podocyte structure and function due to genetic variants become clinically manifest. Therapeutic strategies aimed at minimizing mismatch between these factors may prove clinically useful.

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Section: Discussionmentioning

confidence: 99%

Podocyte number and density changes during early human life

et al. 2016

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“…Correct assembly of the glomerular vasculature is required for filtration barrier function (Bartlett et al, 2016). At p17, Tfeb iECÀ/À kidneys were smaller (% area of Tfeb iECÀ/À mice versus control 72.6 AE 7.9%; mice n = 3, P < 0.01), characterized by poorly developed glomeruli ( Fig EV3B) and reduced volumes (20.53 AE 2.50 × 10 4 lm 3 for control mice and 14.43 AE 3.27 × 10 4 lm 3 for Tfeb iECÀ/À ; mice n = 3, P < 0.002).…”

Section: Tfeb Is Involved In Retinal and Renal Vascular Maturation Afmentioning

confidence: 99%

TFEB controls vascular development by regulating the proliferation of endothelial cells

et al. 2018

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Transcription factor TFEB is thought to control cellular functions—including in the vascular bed—primarily via regulation of lysosomal biogenesis and autophagic flux. Here, we report that TFEB also orchestrates a non‐canonical program that controls the cell cycle/VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB depletion halts proliferation at the G1‐S transition by inhibiting the CDK4/Rb pathway. TFEB‐deficient cells attempt to compensate for this limitation by increasing VEGFR2 levels at the plasma membrane via microRNA‐mediated mechanisms and controlled membrane trafficking. TFEB stimulates expression of the miR‐15a/16‐1 cluster, which limits VEGFR2 transcript stability and negatively modulates expression of MYO1C, a regulator of VEGFR2 trafficking to the cell surface. Altered levels of miR‐15a/16‐1 and MYO1C in TFEB‐depleted cells cause increased expression of plasma membrane VEGFR2, but in a manner associated with low signaling strength. An endothelium‐specific Tfeb‐knockout mouse model displays defects in fetal and newborn mouse vasculature caused by reduced endothelial proliferation and by anomalous function of the VEGFR2 pathway. These previously unrecognized functions of TFEB expand its role beyond regulation of the autophagic pathway in the vascular system.

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“…Diabetic vascular dysfunction also affects various other organs and tissues in extremities, heart, nerves, wounds and kidneys. The contribution of the Ang–Tie system to the pathogenesis of ocular and diabetes-associated vascular diseases is a field of intense research [117,120]. …”

Section: Ang–tie System In Vascular Diseasesmentioning

confidence: 99%

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

Eklund¹,

Kangas²,

2016

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Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases.

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Vascular Growth Factors and Glomerular Disease

Cited by 93 publications

References 150 publications

Podocyte number and density changes during early human life

Podocyte number and density changes during early human life

TFEB controls vascular development by regulating the proliferation of endothelial cells

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

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