Distribution of extracellular matrix receptors in various forms of glomerulonephritis

Kenichi Shikata, Hirofumi Makino, Shigeru Morioka, Tadatoshi Kashitani, Kyoji Hirata, Zensuke Ota, Jun Wada, Yashpal S. Kanwar

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Integrins are heterodimeric transmembrane receptor glycoproteins consisting of α and β subunits that mediate adhesion and interactions between cells and extracellular matrix. Such interactions may be perturbed in various pathologic states, resulting in the altered phenotypic expressions of the integrins in affected tissues. To ascertain the alterations in integrins in various renal diseases, their distribution was investigated in different forms of glomerulonephritis by indirect immunofluorescence and immunoelectron microscopy using specific antibodies directed against β1 integrins and integrin αvβ3 (vitronectin receptor). In addition, the distribution of certain extracellular matrix components (ie, fibronectin, vitronectin, and type IV collagen) was examined. Integrin β1 and αvβ3 were highly expressed in proliferating mesangial cells in immunoglobulin A nephropathy, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. Their putative ligands (ie, fibronectin, vitronectin, and type IV collagen) also were increased in the expanded mesangial regions. In immunoglobulin A nephropathy, integrin β1 and αvβ3 were seen by immunoelectron microscopy to be localized to the mesangial cell membranes in close proximity to the immune complex deposits; however, fibronectin and vitronectin immunoreactivities were observed in the mesangial immune complex deposits. Similarly, vitronectin also was detected in the immune complex deposits of other forms of proliferative nephritis, ie, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. In diffuse proliferative lupus nephritis, the cellular crescents displayed immunoreactivity toward integrin αvβ3 and vitronectin. In nonimmune complex glomerular disease associated with nephrotic syndrome (ie, minimal change nephrotic syndrome), integrin α3β1, which normally has a linear capillary distribution, was decreased. In immune complex nephritis associated with nephrotic syndrome (ie, membranous nephropathy), integrin α3β1 immunoreactivity was focally disrupted and capillary loops displayed a discontinuous linear distribution. Finally, in membranous nephropathy, immunoreactivity toward vitronectin was accentuated in immune complex deposits. The differential altered distributions of the integrins and of their ligands may be reflective of mesangial cell proliferative activity in certain forms of glomerulonephritis, while in other forms of glomerular diseases, the decreased immunoreactivity of integrin α3β1 may be related to the glomerular capillary wall alterations associated with proteinuric states.

Original languageEnglish
Pages (from-to)680-688
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume25
Issue number5
DOIs
Publication statusPublished - May 1995

Keywords

  • Integrins
  • fibronectin
  • glomerulonephritis
  • type IV collagen
  • vitronectin
  • vitronectin receptor

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Distribution of extracellular matrix receptors in various forms of glomerulonephritis'. Together they form a unique fingerprint.

  • Cite this