Epithelial-to-mesenchymal transition in early transplant tubulointerstitial damage.
It is unknown whether epithelial-to-mesenchymal transition (EMT) leads to tubulointerstitial fibrosis in renal transplants. In this study, interstitial fibrosis and markers of EMT were followed in protocol transplant biopsies in 24 patients. Tubulointerstitial damage (TID) increased from 34 to 54% between 1 and 3 mo after transplantation. Detection of EMT depended on the marker used; low levels of alpha-smooth muscle actin were found in 61% of biopsies, but the less specific marker S100 calcium binding protein-A4 (also known as Fsp1) suggested a higher incidence of EMT. The presence or development of TID did not correlate with EMT but instead significantly correlated with subclinical immune activity (P < 0.05). Among biopsies showing TID, microarray analysis revealed differential regulation of 127 genes at 1 mo and 67 genes at 3 mo compared with baseline; these genes were predominantly associated with fibrosis, tissue remodeling, and immune response. Of the 173 EMT-associated genes interrogated, however, only 8.1% showed an expression pattern consistent with EMT at 1 mo and 6.3% at 3 mo. The remainder were not differentially altered, or their changes in expression were opposite those expected to promote EMT. Quantitative reverse transcriptase-PCR revealed that the expression pattern of 12 EMT-associated genes was inconsistent over time, opposite that expected, or consistent with subclinical rejection or inflammation. In conclusion, EMT does not seem to play a significant role in the development of early allograft fibrosis.
Vitalone
Matthew J
MJ
Centre for Transplant and Renal Research, University of Sydney, Westmead Hospital, Sydney, Australia.
O'Connell
Philip J
PJ
Jimenez-Vera
Elvira
E
Yuksel
Aysen
A
Wavamunno
Moses
M
Fung
Caroline L-S
CL
Chapman
Jeremy R
JR
Nankivell
Brian J
BJ
D000328:Adult; D054338:Cell Transdifferentiation; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009400:Nephrosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019459:Urothelium / Q000166:cytology