Distribution of αvβT3, αvβTB5 Integrins and the Integrin Associated Protein — IAP (CD47) in Human Glomerular Diseases

Abstract

The a v integrins present on the membrane of numerous cells, mediate attachment to matrix proteins, cell proliferation, migration and survival. We studied the expression of a v integrins and CD47 (a 0 3 chain integrin associated protein) in various forms of glomerulonephritis (GN) characterized by mesangial proliferation and/or increased mesangial matrix. In normal glomeruli, epithelial cells expressed avp3, avP5 and CD47; endothelial cells expressed asp1 and C D 4 7 ; mesangial cells expressed avp5, CD47, and to a less extent avp3. In acute post infectious GN (APIGN), membranoproliferative GN (MPGN) and diabetic nephropathy (DN), we observed that the p3 chain, normally expressed by mesangial cells, was not detectable in the mesangium while its expression by epithelial cells was not modified. Parallel to the disappearance of avD3, the CD47 expression was decreased on the mesangial cells in MPGN, APIGN and DN. The expression of avpS was clearly increased on podocytes and on proliferating mesangial cells in APIGN. By contrast, the mesangial expression of avP5 was normal or decreased in DN. The a5 chain of integrin, absent on normal mesangial cell, was expressed on proliferating mesangial cells in MPGN and APIGN.Thus, we observed modifications of avp3 and avp5 expression during human GN. The modulations of avp3 and avp5 expression differed according to the different glomerular cell types and were not parallel in glomerular cells: avp3 was decreased (and avp5 unchanged) on proliferating mesangial cells and avpS was increased (and avp3 unchanged) in podocytes. This may reflect the existence of two distinct regulatory pathways.

Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney

“…Secreted CCN1, which may be quantified by CCN1 staining at the cytoplasm, can act on glomerular cells in a GBM-bound form, since CCN1 has a high affinity for heparan sulfate proteoglycans (37), a major component of the GBM (8). Furthermore, CCN1 interacts with a variety of integrins (3,9,14,19,28), e.g., acting through integrin ␣ v ␤ 3 on endothelial cells and through ␣ v ␤ 5 on fibroblasts (9,14), both of which are expressed in mesangial cells and podocytes (10). It was recently reported that production of vascular endothelial growth factor A, a homodimeric glycoprotein of 48 kDa, from podocytes is required for mesangial cell survival in vivo (6), suggesting that secreted factors from podocytes can act on glomerular cells, counteracting against the flow from the capillary lumen to the urinary space.…”

“…The transfer vector along with BacPAK6 viral DNA (Clontech) was delivered into cells by liposome-mediated transfection to obtain a recombinant virus. Sf9 cells grown to 10 6 cells/ml in SFM-II medium were infected with the recombinant virus and incubated for 48 h at 28°C. The conditioned media centrifuged at 5,000 g for 5 min at 4°C were adjusted to 50 mM sodium phosphate buffer (pH 6.0) containing 2 mM EDTA and 1 mM PMSF and applied to a Hitrap SP column (Amersham, Piscataway, NJ) at 4°C.…”

Activated CD47 regulates multiple vascular and stress responses: implications for acute kidney injury and its management

“…In renal diseases including acute postinfectious glomerulonephritis (GN), membranoproliferative GN, and diabetic nephropathy, CD47 expression decreased in mesangial cells (31). CD47 is also markedly decreased during mesangiolysis, but increased in mesangial cells in the restoration stage (60).…”

“…In cell culture or with injury, TSP1 is secreted by kidney mesangial cells, a process that can be suppressed by nitric oxide (NO) pro-drugs (96). CD47 is expressed in several renal cell types including epithelial, endothelial, and mesangial cells (31) but not in podocytes (60). It is also expressed in proximal tubular HK-2 cells (7).…”

Anti-Inflammatory Effects of αv Integrin Antagonism in Acute Kidney Allograft Rejection

“…[25][26][27] In ischemic rat kidneys ␤ 1 and ␣ v ␤ 3 were found to be localized in proximal and distal tubules and endothelium. 27 Also different forms of glomerulonephritis were found to be associated with modifications in their ␣ v integrin expression: the distal tubular expression of ␤ 3 was increased, and a de novo appearance of ␣ v ␤ 3 and ␣ v ␤ 5 on proximal tubular cells in comparison to normal kidneys was noticed 24,43 ; ␣ v ␤ 6 , which is exclusively expressed by epithelial cells, was elevated in the kidney epithelium of patients with membranous glomerulonephritis, IgA nephropathy, and in acute and chronic rejection of human kidney allografts. 44, 45 By immunostaining we could show the increased expression of ␣ v ␤ 3 in rejecting rat kidney allografts, in peritubular capillaries, on the endothelial surface of preglomerular arteries and in tubular epithelial cells in comparison to normal F344 kidneys as well as its presence in the intragraft perivascular cellular infiltrate.…”