Increased expression of cell adhesion kinase beta in human and rat crescentic glomerulonephritis.
Cell adhesion kinase beta (CAKbeta, also known as Pyk2/CadTK/RAFTK) is the second member of the focal adhesion kinase (FAK) subfamily. We examined the expression of CAKbeta in various human glomerulopathies by immunohistochemistry. Although CAKbeta expression in the normal kidney is confined to the brush border of the proximal tubule with no detectable glomerular staining, we found that glomerular crescents strongly expressed this kinase. Expression of CAKbeta was prominent in cellular crescents but was minimal in fibrocellular or fibrous crescents. Serial section analysis revealed that most CAKbeta-expressing cells were positive for cytokeratin but were negative for CD68 (a macrophage marker), suggesting that CAKbeta was expressed by parietal epithelium in the crescents. We also examined CAKbeta expression in a rat model of crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody. Similar to human nephritis, enhanced expression of CAKbeta in glomerular crescents was apparent. Increased expression of CAKbeta also was confirmed by anti-CAKbeta immunoblotting and by real-time quantitative polymerase chain reaction. Previous studies have shown that CAKbeta is activated by various stimuli regulating cell growth and survival. Although our findings do not determine whether or not increased expression of CAKbeta is a primary event for the development of crescentic glomerulonephritis, further understanding of this pathway may be important to gain novel insights into the factors that promote crescent formation.
Takagi
Chieko
C
Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Ueki
Kazue
K
Ikeuchi
Hidekazu
H
Kuroiwa
Takashi
T
Kaneko
Yoriaki
Y
Tsukada
Yoshito
Y
Maezawa
Akira
A
Mitaka
Toshihiro
T
Sasaki
Terukatsu
T
Nojima
Yoshihisa
Y
D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D005260:Female; D051418:Focal Adhesion Kinase 2; D015971:Gene Expression Regulation, Enzymologic; D005921:Glomerulonephritis / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496054:Ptk2b protein, rat