Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.
Inhibition of MMPs early after transplantation reduced the development and progression of CAN but promoted CAN if initiated at later stages. Thus, MMPs are involved in the development and progression of CAN.
The purpose of the study was to determine whether exercise would activate JNK in the heart and whether chronic exercise training would alter the response. Untrained rats were familiarized with the treadmill and assigned to one of four groups: low intensity (LI), 10 min, 0%, 15 m/min; medium intensity (MI), 10 min, 0%, 33 m/min; high intensity (HI), 10 min, 25%, 33 m/min; long duration (LD), 30 min, 0%, 15 m/min. Another cohort of rats was subjected to a progressive 6 wk high-intensity training protocol that produced a 12% increase in heart mass. In untrained rats, JNK activity was LI: 1.5 (fold nonrun control), MI: 2.0, HI: 2.5, LD: 1.25 immediately after a single bout of exercise. In trained rats, no activation of JNK above baseline was detected after either a 10-min or 1-h bout of exercise. We concluded that treadmill exercise activates JNK in the rat heart in an intensity-dependent manner and that chronic training abrogates the myocardial JNK response to a bout of exercise.
Our data suggest that dihydrotestosterone mediates the adverse effects of androgens on chronic allograft nephropathy. The inhibition of androgens improves long-term allograft outcome after kidney transplantation.
In the present study we investigated whether donor gender or the effects of sex hormones play the greater role in the development of chronic allograft nephropathy. Kidneys of male and female Fisher rats were orthotopically transplanted into castrated male Lewis recipients. Animals were treated with testosterone, estradiol, or vehicle and the kidneys were harvested 20 weeks after transplantation for histological, immunohistological, and molecular analysis. Testosterone treatment resulted in increased proteinuria and profound glomerulosclerosis, irrespective of donor gender. In addition, mRNA levels of transforming growth factor-PI (TGF-01) and platelet-derived growth factor-A and B (PDGF-A and B) chains were enhanced in these allografts. Estradiol reduced glomerulosclerosis and mononuclear cell infiltration in allografts of both genders that paralleled a decreased mRNA expression of TGF-P1, PDGF-A and B. No donor genderrelated differences were noted in vehicle-treated animals. Our findings demonstrate that sex hormones rather than donor gender have a significant impact on chronic allograft nephropathy.
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