Laminin α4-null mutant mice develop chronic kidney disease with persistent overexpression of platelet-derived growth factor

Christine K. Abrass, Kim M. Hansen, Bruce Patton

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Each extracellular matrix compartment in the kidney has a unique composition, with regional specificity in the expression of various laminin isoforms. Although null mutations in the majority of laminin chains lead to specific developmental abnormalities in the kidney, Lama4-/- mice have progressive glomerular and tubulointerstitial fibrosis. These mice have a significant increase in expression of platelet-derived growth factor (PDGF)-BB, PDGF-DD, and PDGF receptor β in association with immature glomerular and peritubular capillaries. In addition, mesangial cell exposure to α4-containing laminins, but not other isoforms, results in down-regulation of PDGF receptor mRNA and protein, suggesting a direct effect of LN411/LN421 on vessel maturation. Given the known role of overexpression of PDGF-BB and PDGF-DD on glomerular and tubulointerstitial fibrosis , these data suggest that failure of laminin α4-mediated down-regulation of PDGF activity contributes to the progressive renal lesions in this animal model. Given the recent demonstration that individuals with laminin β4 mutations develop cardiomyopathy, these findings may be relevant to kidney disease in humans.

Original languageEnglish (US)
Pages (from-to)839-849
Number of pages11
JournalAmerican Journal of Pathology
Volume176
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Platelet-Derived Growth Factor
Laminin
Chronic Renal Insufficiency
Platelet-Derived Growth Factor Receptors
Kidney
Protein Isoforms
Fibrosis
Down-Regulation
Mutation
Mesangial Cells
Kidney Diseases
Cardiomyopathies
Extracellular Matrix
Animal Models
Messenger RNA
Proteins
platelet-derived growth factor BB

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Laminin α4-null mutant mice develop chronic kidney disease with persistent overexpression of platelet-derived growth factor. / Abrass, Christine K.; Hansen, Kim M.; Patton, Bruce.

In: American Journal of Pathology, Vol. 176, No. 2, 02.2010, p. 839-849.

Research output: Contribution to journalArticle

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