Up-regulation of Intragraft Gene Expression of Bcl-xL in Response to Injuries to Renal Allograft / 대한신장학회잡지

ABSTRACT

BACKGROUND: Bcl-xL and bax act as checkpoints of the apoptotic cell death. Although apoptosis is one of major mechanism of cell death in renal allografts inflicted by various events, the role of bcl-xL and bax in kidney transplantation has not been characterized yet. We therefore studied intragraft expression of bcl-x and bax and its clinical significance in renal transplantation. METHODS: We localized the expression of bcl-x, bcl-xS and bax proteins by immunohistochemistry, and measured the magnitude of the gene transcription of bax and bcl-xL by semi-quantitative RT-PCR in 37 implantation allograft biopsies(18 from 9 cadaveric donors, 19 from living donors), and 17 biopsies from patients undergoing acute rejection(AR). RESULTS: Immunoreactivities for bax, bcl-x, and bcl-xS were observed in tubular epithelial cells but not in glomeruli and vessels in implantation and AR biopsies. The infiltrating lymphocytes in AR expressed bax and bcl-xS but not for bcl-x. Comparing the intragraft gene transcript level of each allograft of a pair of recipients, who received graft from the same cadaveric donor, showed a higher bcl-xL in the patients with a higher concentration of postoperative 7th day serum creatinine. The transcript level of bcl-xL was higher in the Banff grade II and III AR biopsies than in the borderline or grade I AR, and also higher in steroid-resistant AR than in steroid-responsive patients. CONCLUSION: These results implicated the apoptotic death of infiltrating lymphocytes during rejection, and the compensatory up-regulation of bcl-xL in response to various apoptotic stimuli occurring in renal allografts.