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Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling

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Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling. / Farber, Gregory; Hurtado, Romulo; Loh, Sarah; Monette, Sébastien; Mtui, James; Kopan, Raphael; Quaggin, Susan; Meyer-Schwesinger, Catherine; Herzlinger, Doris; Scott, Rizaldy P; Blobel, Carl P.

In: ANGIOGENESIS, Vol. 21, No. 2, 05.2018, p. 335-347.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Farber, G, Hurtado, R, Loh, S, Monette, S, Mtui, J, Kopan, R, Quaggin, S, Meyer-Schwesinger, C, Herzlinger, D, Scott, RP & Blobel, CP 2018, 'Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling', ANGIOGENESIS, vol. 21, no. 2, pp. 335-347. https://doi.org/10.1007/s10456-018-9599-4

APA

Farber, G., Hurtado, R., Loh, S., Monette, S., Mtui, J., Kopan, R., Quaggin, S., Meyer-Schwesinger, C., Herzlinger, D., Scott, R. P., & Blobel, C. P. (2018). Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling. ANGIOGENESIS, 21(2), 335-347. https://doi.org/10.1007/s10456-018-9599-4

Vancouver

Farber G, Hurtado R, Loh S, Monette S, Mtui J, Kopan R et al. Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling. ANGIOGENESIS. 2018 May;21(2):335-347. https://doi.org/10.1007/s10456-018-9599-4

Bibtex

@article{ec38a615858e4551b9bb65dc8abeaae8,
title = "Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling",
abstract = "The principal function of glomeruli is to filter blood through a highly specialized filtration barrier consisting of a fenestrated endothelium, the glomerular basement membrane and podocyte foot processes. Previous studies have uncovered a crucial role of endothelial a disintegrin and metalloprotease 10 (ADAM10) and Notch signaling in the development of glomeruli, yet the resulting defects have not been further characterized nor understood in the context of kidney development. Here, we used several different experimental approaches to analyze the kidneys and glomeruli from mice lacking ADAM10 in endothelial cells (A10ΔEC mice). Scanning electron microscopy of glomerular casts demonstrated enlarged vascular diameter and increased intussusceptive events in A10ΔEC glomeruli compared to controls. Consistent with these findings, genes known to regulate vessel caliber (Apln, AplnR and Vegfr3) are significantly upregulated in A10ΔEC glomeruli. Moreover, transmission electron microscopy revealed the persistence of diaphragms in the fenestrae of A10ΔEC glomerular endothelial cells, which was corroborated by the elevated expression of the protein PLVAP/PV-1, an integral component of fenestral diaphragms. Analysis of gross renal vasculature by light sheet microscopy showed no major alteration of the branching pattern, indicating a localized importance of ADAM10 in the glomerular endothelium. Since intussusceptions and fenestrae with diaphragms are normally found in developing, but not mature glomeruli, our results provide the first evidence for a crucial role of endothelial ADAM10, a key regulator of Notch signaling, in promoting the development and maturation of the glomerular vasculature.",
keywords = "Journal Article",
author = "Gregory Farber and Romulo Hurtado and Sarah Loh and S{\'e}bastien Monette and James Mtui and Raphael Kopan and Susan Quaggin and Catherine Meyer-Schwesinger and Doris Herzlinger and Scott, {Rizaldy P} and Blobel, {Carl P}",
year = "2018",
month = may,
doi = "10.1007/s10456-018-9599-4",
language = "English",
volume = "21",
pages = "335--347",
journal = "ANGIOGENESIS",
issn = "0969-6970",
publisher = "Springer Netherlands",
number = "2",

}

RIS

TY - JOUR

T1 - Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling

AU - Farber, Gregory

AU - Hurtado, Romulo

AU - Loh, Sarah

AU - Monette, Sébastien

AU - Mtui, James

AU - Kopan, Raphael

AU - Quaggin, Susan

AU - Meyer-Schwesinger, Catherine

AU - Herzlinger, Doris

AU - Scott, Rizaldy P

AU - Blobel, Carl P

PY - 2018/5

Y1 - 2018/5

N2 - The principal function of glomeruli is to filter blood through a highly specialized filtration barrier consisting of a fenestrated endothelium, the glomerular basement membrane and podocyte foot processes. Previous studies have uncovered a crucial role of endothelial a disintegrin and metalloprotease 10 (ADAM10) and Notch signaling in the development of glomeruli, yet the resulting defects have not been further characterized nor understood in the context of kidney development. Here, we used several different experimental approaches to analyze the kidneys and glomeruli from mice lacking ADAM10 in endothelial cells (A10ΔEC mice). Scanning electron microscopy of glomerular casts demonstrated enlarged vascular diameter and increased intussusceptive events in A10ΔEC glomeruli compared to controls. Consistent with these findings, genes known to regulate vessel caliber (Apln, AplnR and Vegfr3) are significantly upregulated in A10ΔEC glomeruli. Moreover, transmission electron microscopy revealed the persistence of diaphragms in the fenestrae of A10ΔEC glomerular endothelial cells, which was corroborated by the elevated expression of the protein PLVAP/PV-1, an integral component of fenestral diaphragms. Analysis of gross renal vasculature by light sheet microscopy showed no major alteration of the branching pattern, indicating a localized importance of ADAM10 in the glomerular endothelium. Since intussusceptions and fenestrae with diaphragms are normally found in developing, but not mature glomeruli, our results provide the first evidence for a crucial role of endothelial ADAM10, a key regulator of Notch signaling, in promoting the development and maturation of the glomerular vasculature.

AB - The principal function of glomeruli is to filter blood through a highly specialized filtration barrier consisting of a fenestrated endothelium, the glomerular basement membrane and podocyte foot processes. Previous studies have uncovered a crucial role of endothelial a disintegrin and metalloprotease 10 (ADAM10) and Notch signaling in the development of glomeruli, yet the resulting defects have not been further characterized nor understood in the context of kidney development. Here, we used several different experimental approaches to analyze the kidneys and glomeruli from mice lacking ADAM10 in endothelial cells (A10ΔEC mice). Scanning electron microscopy of glomerular casts demonstrated enlarged vascular diameter and increased intussusceptive events in A10ΔEC glomeruli compared to controls. Consistent with these findings, genes known to regulate vessel caliber (Apln, AplnR and Vegfr3) are significantly upregulated in A10ΔEC glomeruli. Moreover, transmission electron microscopy revealed the persistence of diaphragms in the fenestrae of A10ΔEC glomerular endothelial cells, which was corroborated by the elevated expression of the protein PLVAP/PV-1, an integral component of fenestral diaphragms. Analysis of gross renal vasculature by light sheet microscopy showed no major alteration of the branching pattern, indicating a localized importance of ADAM10 in the glomerular endothelium. Since intussusceptions and fenestrae with diaphragms are normally found in developing, but not mature glomeruli, our results provide the first evidence for a crucial role of endothelial ADAM10, a key regulator of Notch signaling, in promoting the development and maturation of the glomerular vasculature.

KW - Journal Article

U2 - 10.1007/s10456-018-9599-4

DO - 10.1007/s10456-018-9599-4

M3 - SCORING: Journal article

C2 - 29397483

VL - 21

SP - 335

EP - 347

JO - ANGIOGENESIS

JF - ANGIOGENESIS

SN - 0969-6970

IS - 2

ER -