TY - JOUR
T1 - Distribution of integrin subunits in human diabetic kidneys
AU - Jin, Dong Kyu
AU - Fish, Alfred J.
AU - Wayner, Elizabeth A.
AU - Mauer, Michael
AU - Setty, Suman
AU - Tsilibary, Effie
AU - Kim, Youngki
PY - 1996/12
Y1 - 1996/12
N2 - Integrins are cell-surface protein receptors that participate in cell adhesion to multiple extracellular matrix ligands, and consist of a and β chain heterodimers. This study examined altered integrin distribution in diabetic nephropathy by investigating 12 human diabetic kidney biopsies, which were compared with normal human kidney. Diabetic nephropathy is characterized by mesangial expansion and progressive thickening of the glomerular basement membrane. Based on morphometric studies of mesangial expansion, diabetic nephropathy was determined to be moderate or severe. Three different patterns (P) of altered intensity of integrin staining were observed. In the mesangial integrin P, the intensity of integrin subunit staining of mesangial cells (α1, α2, α3, β1, αv, αvβ5) was increased in moderate diabetic nephropathy and further increased in severe diabetic nephropathy. In the epithelial integrin P, integrin subunits localized to epithelial cells (αv, β3, αvβ3, αvβ5) were increased to the same extent in moderate and severe diabetic nephropathy. In the endothelial integrin P, integrin subunits localized to endothelial cells (α3, α5, α6, β1) were increased in moderate diabetic nephropathy but returned to normal kidney staining intensity in severe diabetic nephropathy. From these observations, it was concluded that there is significant alteration in the expression of integrin subunits in diabetic nephropathy that is related to the severity of diabetic mesangial expansion. Additionally, the spectrum of integrin subunit alteration appears to be unique to individual glomerular cell types. Given the role of integrins in cell-surface interactions with extracellular matrix components, abnormalities in the expression of these molecules may be important in the pathogenesis of diabetic nephropathy.
AB - Integrins are cell-surface protein receptors that participate in cell adhesion to multiple extracellular matrix ligands, and consist of a and β chain heterodimers. This study examined altered integrin distribution in diabetic nephropathy by investigating 12 human diabetic kidney biopsies, which were compared with normal human kidney. Diabetic nephropathy is characterized by mesangial expansion and progressive thickening of the glomerular basement membrane. Based on morphometric studies of mesangial expansion, diabetic nephropathy was determined to be moderate or severe. Three different patterns (P) of altered intensity of integrin staining were observed. In the mesangial integrin P, the intensity of integrin subunit staining of mesangial cells (α1, α2, α3, β1, αv, αvβ5) was increased in moderate diabetic nephropathy and further increased in severe diabetic nephropathy. In the epithelial integrin P, integrin subunits localized to epithelial cells (αv, β3, αvβ3, αvβ5) were increased to the same extent in moderate and severe diabetic nephropathy. In the endothelial integrin P, integrin subunits localized to endothelial cells (α3, α5, α6, β1) were increased in moderate diabetic nephropathy but returned to normal kidney staining intensity in severe diabetic nephropathy. From these observations, it was concluded that there is significant alteration in the expression of integrin subunits in diabetic nephropathy that is related to the severity of diabetic mesangial expansion. Additionally, the spectrum of integrin subunit alteration appears to be unique to individual glomerular cell types. Given the role of integrins in cell-surface interactions with extracellular matrix components, abnormalities in the expression of these molecules may be important in the pathogenesis of diabetic nephropathy.
KW - Cell adhesion receptors
KW - Extracellular matrix
KW - Glomerular basement membrane
KW - Integrin heterodimers
KW - Mesangium
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M3 - Article
C2 - 8989742
AN - SCOPUS:9844241050
SN - 1046-6673
VL - 7
SP - 2636
EP - 2645
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 12
ER -