α8 Integrin in glomerular mesangial cells and in experimental glomerulonephritis

Hartner, Andrea; Schöcklmann, Harald O.; Pröls, Felicitas; Müller, Ulrich; Sterzel, R. Bernd

doi:10.1046/j.1523-1755.1999.00662.x

Cited by 78 publications

(87 citation statements)

References 21 publications

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“…Mesangial cells express a broader range of ␤ 1 integrins, including (25,31,32), and most ␣-specific antagonists affected adhesion of these cells to the TSRs. This suggests that the TSRs are pan-specific ligands for ␤ 1 integrins.…”

Section: Figmentioning

confidence: 99%

Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1

Calzada

Annis

Zeng

et al. 2004

Journal of Biological Chemistry

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In addition to the three known ␤ 1 integrin recognition sites in the N-module of thrombospondin-1 (TSP1), we found that ␤ 1 integrins mediate cell adhesion to the type 1 and type 2 repeats. The type 1 repeats of TSP1 differ from typical integrin ligands in that recognition is pan-␤ 1 -specific. Adhesion of cells that express one dominant ␤ 1 integrin on immobilized type 1 repeats is specifically inhibited by antagonists of that integrin, whereas adhesion of cells that express several ␤ 1 integrins is partially inhibited by each ␣-subunit-specific antagonist and completely inhibited by combining the antagonists. ␤ 1 integrins recognize both the second and third type 1 repeats, and each type 1 repeat shows pan-␤ 1 specificity and divalent cation dependence for promoting cell adhesion. Adhesion to the type 2 repeats is less sensitive to ␣-subunit antagonists, but a ␤ 1 blocking antibody and two disintegrins inhibit adhesion to immobilized type 2 repeats. ␤ 1 integrin expression is necessary for cell adhesion to the type 1 or type 2 repeats, and ␤ 1 integrins bind in a divalent cation-dependent manner to a type 1 repeat affinity column. The widely used TSP1 function blocking antibody A4.1 binds to a site in the third type 2 repeat. A4.1 proximally inhibits ␤ 1 integrin-dependent adhesion to the type 2 repeats and indirectly inhibits integrin-dependent adhesion mediated by the TSP1 type 1 repeats. Although antibody A4

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Section: Figmentioning

confidence: 99%

Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1

Calzada

Annis

Zeng

et al. 2004

Journal of Biological Chemistry

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“…Rabbit polyclonal antiserum to ␣8 integrin was used at a dilution of 1:500, as described previously (4). Monoclonal antibodies to ␣-smooth muscle actin and proliferating cell nuclear antigen (PCNA) (both from Dako Diagnostika, Hamburg, Germany) were used at a dilution of 1:500, after blocking of endogenous mouse IgG with a MOM kit (Linaris, Wertheim, Germany).…”

Section: Antibodiesmentioning

confidence: 99%

“…In the adult kidney, ␣8 expression was noted in glomeruli and renal arterioles (3). In immunohistochemical studies, we demonstrated that glomerular expression of ␣8 was restricted to the mesangium in human, rat, and mouse kidneys (4). ␣8␤1 is a receptor for fibronectin, vitronectin, tenascin-C (5), osteopontin (6), and a novel ligand termed nephronectin (7).…”

mentioning

confidence: 99%

Glomerular and Renal Vascular Structural Changes in α8 Integrin-Deficient Mice

Haas¹,

Amann²,

Schittny³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the ␣8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. ␣8-deficient (␣8Ϫ/Ϫ) 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 ␣8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of ␣8Ϫ/Ϫ mice would be completely normal. Therefore, the renal phenotype of adult ␣8Ϫ/Ϫ mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. ␣8Ϫ/Ϫ 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 ␣8Ϫ/Ϫ mice. Quantitative morphologic analyses revealed that the glomeruli of ␣8Ϫ/Ϫ 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 ␣8 ligand fibronectin) was expanded in ␣8Ϫ/Ϫ mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of ␣8Ϫ/Ϫ mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor ␣2 integrin in ␣8Ϫ/Ϫ mice. The glomerular capillary length density was significantly greater in ␣8Ϫ/Ϫ mice than in wild-type mice. Cortical arterial vessel walls were not altered in ␣8Ϫ/Ϫ mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of ␣8, glomerular and renal vascular alterations in ␣8Ϫ/Ϫ mice were relatively mild. Only aged ␣8Ϫ/Ϫ mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of ␣8 can be largely compensated for, at least in younger ␣8Ϫ/Ϫ 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 ␣2 contribute to maintaining the glomerular structure in ␣8Ϫ/Ϫ mice. The compensatory mechanisms involved will be the subject of future research.Integrins are heterodimeric transmembrane glycoproteins, each consisting of two noncovalently linked chains, the ␣ and ␤ subunits. Eighteen ␣ and eight ␤ chains have been identified; they combine to form 24 integrin receptor types (1). Cellmatrix interactions mediated mainly by integrins of the ␤1 family play important roles in embryogenesis and maintenance of the normal structure and function of organs, including the kidney (1). Furthermore, many human and experimental renal diseases are associated with altered expression of integrins (2), pointing to an important role for integrins in the development and/or progress...

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“…Existent evidence indicates a link between a8b1 integrin expression and cardiac, lung, kidney and liver fibrosis. [12][13][14] When we look at the pathological conditions in which a8 expression is increased, we see that there is one property in common. In these fibrotic organs, tensile forces are increased.…”

Section: Tensegrin In Contextmentioning

confidence: 99%

“…13 Stellate cells of the liver, lung alveolar myofibroblasts, and lung interstitial cells are other cell types with intense a8 integrin leads to reduced membrane-anchored RhoA, a hallmark of RhoA activity 51 ( Fig. 2A).…”

Section: Lessons From Parallel Universesmentioning

confidence: 99%

Tensegrin in context

Zargham

2010

Cell Adhesion & Migration

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α8 Integrin in glomerular mesangial cells and in experimental glomerulonephritis

Cited by 78 publications

References 21 publications

Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1

Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1

Glomerular and Renal Vascular Structural Changes in α8 Integrin-Deficient Mice

Tensegrin in context

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