Exercise rescued chronic kidney disease by attenuating cardiac hypertrophy through the cardiotrophin-1 -> LIFR/gp 130 -> JAK/STAT3 pathway.
BACKGROUND
Chronic kidney disease (CKD) is usually associated with cardiac apoptosis and/or cardiac hypertrophy. We hypothesized that exercise can reduce the CKD-induced cardiac damage.


METHODS AND RESULTS
The doxorubicin-induced CKD (DRCKD) model was used in rats to compare two exercise models: 60-min running and 60-min swimming. Results indicated that in healthy normal groups, the signals cardiotrophin-1 (CT-1), interleukin 6 (IL-6), leukaemia inhibitory factor receptor (LIFR), and gp130 were upregulated and janus kinase (JAK) and signal transducer and activation of transcription (STAT) were downregulated by both exercises. In contrast, all signals were highly upregulated in CKD. After exercise training, all signals (CT-1, IL-6, LIFR, gp130, and STAT) were downregulated, with JAK being only slightly upregulated in the running group but not in the swimming group. The myocyte death pathway (CT-1/IL-6 → LIFR/gp130 → PI3K → Akt → Bad) was excluded due to no change found for Bad. Nitric oxide (NO; normal, 15.63 ± 0.86 µmol/l) was significantly suppressed in CKD rats (2.95 ± 0.32 µmol/l), and both running and swimming training highly upregulated the NO level to 30.33 ± 1.03 µmol/l and 27.82 ± 2.47 µmol/l in normal subjects and 24.0 ± 3.2 µmol/l and 22.69 ± 3.79 µmol/l in the DRCKD rats, respectively. The endothelial progenic cells CD34 were significantly suppressed in DRCKD rats, which were not rescued significantly by exercise. In contrast, the CD 34 cells were only slightly suppressed in the healthy subjects by exercise.


CONCLUSION
Both exercise regimens were beneficial by rescuing cardiac function in CKD victims. Its action mechanism was by way of inhibiting myocyte death and rescuing cardiac hypertrophy.
['Chen|Kuan-Chou|KC|', 'Hsieh|Chiu-Lan|CL|', 'Peng|Chiung-Chi|CC|', 'Peng|Robert Y|RY|']
D000818:Animals D015415:Biomarkers D006332:Cardiomegaly D050822:Cytokine Receptor gp130 D016207:Cytokines D004195:Disease Models, Animal D042783:Endothelial Cells D005081:Exercise Therapy D005919:Glomerular Filtration Rate D053612:Janus Kinases D007668:Kidney D053680:Leukemia Inhibitory Factor Receptor alpha Subunit D008297:Male D032383:Myocytes, Cardiac D051381:Rats D017207:Rats, Sprague-Dawley D051436:Renal Insufficiency, Chronic D012420:Running D050796:STAT3 Transcription Factor D015398:Signal Transduction D013234:Stem Cells D013550:Swimming D013997:Time Factors
Cardiac hypertrophy chronic kidney disease (CKD) doxorubicin