Integrin alpha-v-beta 6 Protein Expression in Human Renal Allograft Biopsies: A Marker of Nephron Distress
Michael Mengel, Samantha Chan, Konrad Famulski, Jessica Chang, Jeff Reeve, Shelia Violette, Paul Weinreb, Philip Halloran. University of Alberta, Edmonton, Canada; Stromedix Inc., Boston; Biogen Idec Inc., Boston
Background: Integrin alpha-v-beta 6 (avb6) is expressed on stressed epithelium, where it activates latent TGF-β1 in the adjacent interstitium.
Design: We stained 123 human renal allograft biopsies for cause (BFC) and 67 six-week protocol biopsies to examine the relationship between avb6 staining and expression of avb6- and TGF-β regulated transcripts, histological lesions, allograft function and outcome.
Results: Staining for avb6 was confined to epithelial cells, and presented two patterns: basolateral and cytoplasmic. The avb6 staining correlated with beta-6-integrin mRNA expression (r=0.41, p<0.001), and with transcripts regulated by avb6 (r=0.29, p=0.004) and TGF-β1 (r=0.28, p<0.001). Staining by avb6 correlated positively with inflammation, fibrosis and atrophy, and showed cytoplasmic accumulation in atrophic tubules, but did not correlate with histological lesions of acute kidney injury. Staining was observed across many injury and disease entities, in early and late biopsies. Cytoplasmic avb6 staining was associated with prior DGF (p=0.029) in protocol biopsies. In early BFC (<1 year post transplantation) with acute kidney injury increased avb6 staining was the only biopsy feature associated with reduced eGFR (table 1). In late BFC with progressive diseases avb6 staining was associated with inferior allograft survival (p=0.006).
Conclusions: Thus avb6 staining is an indicator of epithelial distress and provides mechanistic insights by its association with avb6- and TGF-β regulated transcripts. Increased avb6 protein expression in tubular epithelial cells correlates with dysfunction, and future progression to allograft failure.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 293, Wednesday Afternoon