Evaluation of E-cadherin/catenin complex in primary and secondary glomerulonephritis.
Catenins (alpha-, beta-, gamma-catenin, p120(ctn)) are cytoplasmic proteins initially identified in a complex with E-cadherin (ECD). The latter belongs to a superfamily of transmembrane glycoproteins important for cell adhesion in normal and disease states. Catenins and p120(ctn), in particular, are substrates for growth factor receptor tyrosine kinases. Cell adhesive mechanisms have an impact on cell migration and proliferation and thus are potentially involved in the pathogenesis of glomerulonephritides (GNs). Using appropriate monoclonal antibodies, we investigated the immunohistochemical expression of ECD, alpha-catenin, beta-catenin, gamma-catenin, and p120(ctn) in renal biopsy specimens from 95 patients with primary GN (n = 51) and secondary lupus-associated GN (n = 44). Examined cases were divided into two groups (proliferative [n = 35] and nonproliferative [n = 60] GNs). Among examined molecules, p120(ctn), beta-catenin, and gamma-catenin were expressed more frequently in glomerular epithelial cells, mainly in parietal epithelium (76%, 48%, and 40%, respectively). p120(ctn) and gamma-catenin epithelial expression appeared to be linked closely with proliferative lupus-associated GNs (P = 0.050 and P = 0.029, respectively). Mainly in lupus GNs, with regard to cellular crescents and epithelial cells around microadhesions to Bowman's capsule, p120(ctn) (63% and 73%, respectively), beta-catenin (72% and 75%), and gamma-catenin (75% and 64%) showed the greatest frequencies of positive detection. Mesangial cells were positive only occasionally for the examined molecules. In proliferative lupus GNs, expression of beta-catenin in mesangial cells tended to be prominent (P = 0.066). ECD and alpha-catenin were not expressed in cellular crescents or microadhesions, whereas only ECD was barely detectable in glomerular epithelial cells. In conclusion, expression of beta-catenin, gamma-catenin, and p120(ctn) is focused on glomerular epithelium, as well as on such lesions deriving from it as cellular crescents. This expression probably is linked with epithelial cells' responses to various mitogens, such as growth factors.
Nakopoulou
Lydia
L
Department of Pathology, Medical School, The National and Capodistrian University of Athens, Greece. lnakopou@cc.uoa.gr
Lazaris
Andreas Ch
ACh
Boletis
Ioannis N
IN
Michail
Spyros
S
Giannopoulou
Ioanna
I
Zeis
Petros M
PM
Stathakis
Charalambos P
CP
Davaris
Panagiotis S
PS
D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D010750:Phosphoproteins / Q000378:metabolism; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human