Adenosine receptors are up-regulated in unilateral ureteral obstructed rat kidneys.

Despite recent improvements in immunosuppressive regimens, chronic renal allograft rejection remains a major problem. Tubulointerstitial fibrosis is one of the major histological features of chronic renal allograft rejection, but its exact pathogenic mechanisms are not fully understood. Adenosine present in the normal kidney is significantly elevated in response to cellular damage. The cellular effect of adenosine occurs through 4 known adenosine receptor (AR) subtypes; A(1)AR, A(2A)AR, A(2B)AR, and A(3)AR. All AR subtypes are expressed in the kidney, but the expression of each AR subtype has not been defined under fibrotic conditions. In the present study, we examined AR subtype expression in kidneys that underwent unilateral ureteral obstruction (UUO), a well-characterized model for tubulointerstitial fibrosis. At 5 days after the induction of UUO, we observed α-smooth muscle actin (α-SMA), fibronectin, and collagen I messenger RNA (mRNA) and protein expressions to be significantly up-regulated in the obstructed compared with the sham kidneys, confirming that fibrosis had occurred in the former organs. A(1)AR mRNA expression in the obstructed kidney cortex was 3.2-fold higher than an the sham kidney cortex. Relative to the sham kidney A(2A)AR and A(2B)AR mRNA expressions were also 2.6- and 2.0-fold increased, respectively. A(3)AR mRNA expression in the obstructed kidney cortex was also up-regulated by 3.3-fold. These data demonstrated that all 4 subtypes of AR were increased in the obstructed kidney, which was accompanied by tubulointerstitial fibrosis. Further studies are needed to determine which subtypes of AR play a protective or pathogenic role in tubulointerstitial fibrosis.