Glomerular and renal vascular structural changes in α8 integrin-deficient mice

Christian S. Haas, Kerstin Amann, Johannes Schittny, Barbara Blaser, Ulrich Müller, Andrea Hartner

Research output: Contribution to journalArticlepeer-review

Abstract

Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the α8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. α8-deficient (α8-/-) mice demonstrate reductions in renal mass, which can range from complete renal agenesis to the development of kidneys that are only slightly smaller than wild-type kidneys. No histologic abnormalities of these kidneys have been described. However, considering the prominent expression of α8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of α8-/- mice would be completely normal. Therefore, the renal phenotype of adult α8-/- mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. α8-/- mice displayed a significant reduction in nephron number and an increase in glomerular volume, compared with wild-type control animals. Albuminuria was not different in wild-type and α8-/- mice. Quantitative morphologic analyses revealed that the glomeruli of α8-/- mice were hypercellular, with an increased number of mesangial cells, compared with wild-type mice. Mesangial matrix deposition (as demonstrated for collagen IV and the α8 ligand fibronectin) was expanded in α8-/- mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of α8-/- mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor α2 integrin in α8-/- mice. The glomerular capillary length density was significantly greater in α8-/- mice than in wild-type mice. Cortical arterial vessel walls were not altered in α8-/-mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of α8, glomerular and renal vascular alterations in α8-/- mice were relatively mild. Only aged α8-/- mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of α8 can be largely compensated for, at least in younger α8-/- mice. It is not yet clear whether the occurrence of collagens that are not normally present in glomeruli and the increased abundance of the collagen receptor α2 contribute to maintaining the glomerular structure in α8-/- mice. The compensatory mechanisms involved will be the subject of future research.

Original languageEnglish (US)
Pages (from-to)2288-2296
Number of pages9
JournalJournal of the American Society of Nephrology
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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