Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli.

Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Research Abstract Details 

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Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Abstract Text:

Yashpal S Kanwar,Farhad R Danesh,Sumant S Chugh,

Both endothelial cells and podocytes are sources for laminin alpha1 at the inception of glomerulogenesis and then for laminin alpha5 during glomerular maturation. Why glomerular basement membranes (GBM) undergo laminin transitions is unknown, but this may dictate glomerular morphogenesis. In mice that genetically lack laminin alpha5, laminin alpha5beta2gamma1 is not assembled, vascularized glomeruli fail to form, and animals die at midgestation with neural tube closure and placental deficits. It was previously shown that renal cortices of newborn mice contain endothelial progenitors (angioblasts) and that when embryonic day 12 kidneys are transplanted into newborn kidney, hybrid glomeruli (host-derived endothelium and donor-derived podocytes) result. Reasoning that host endothelium may correct the glomerular phenotype that is seen in laminin alpha5 mutants, alpha5 null embryonic day 12 metanephroi were grafted into wild-type newborn kidney. Hybrid glomeruli were identified in grafts by expression of a host-specific LacZ lineage marker. Labeling of glomerular hybrid GBM with chain-specific antibodies showed a markedly stratified distribution of laminins: alpha5 was found only on the inner endothelial half of GBM, whereas alpha1 located to outer layers beneath mutant podocytes. For measurement of the contribution of host endothelium to hybrid GBM, immunofluorescent signals for laminin alpha5 were quantified: Hybrid GBM contained approximately 50% the normal alpha5 complement as wild-type GBM. Electron microscopy of glomerular hybrids showed vascularization, but podocyte foot processes were absent. It was concluded that (1) endothelial and podocyte-derived laminins remain tethered to their cellular origin, (2) developing endothelial cells contribute large amounts of GBM laminins, and (3) podocyte foot process differentiation may require direct exposure to laminin alpha5.

Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Publishing Authors By Initials

YS Kanwar,FR Danesh,SS Chugh,

For similar surgical procedures, operative: transplantation: transplantation, homologous research abstracts see: surgical procedures, operative: transplantation: transplantation, homologous research

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Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of the American Society of Nephrology : JA

VOLUME: 18

Page Numbers: 2285-93

Journal Abbreviation: J. Am. Soc. Nephrol.

ISSN: 1046-6673

DAY: 28

MONTH: 06

YEAR: 2007

Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9013836

Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Keywords Mesh Terms:

KEYWORDS: Transplantation, Homologous

MESH TERMS: ultrastructure

Chemical & Substance for Abstract: Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli. Information

Substance Name: laminin alpha5

Registry Number: 0

Grant and Affiliation Information for Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli.

AFFILIATION: Department of Anatomy and Cell Biology, University of Kansas Medical Center, MS 3038, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. dabrahamson@kumc.edu

Country: United States

AGENCY: United States NCRR

GRANT: RR016475

ACRONYM: RR

MEDLINETA: J Am Soc Nephrol

REFSOURCE: J Am Soc Nephrol. 2007 Aug;18(8):2215-7

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