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.


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.


CONCLUSIONS
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.
Taipei Medical University, Taipei, Taiwan.
Kuan-Chou
KC
Chen
Chiu-Lan
CL
Hsieh
Chiung-Chi
CC
Peng
Robert Y
RY
Peng
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D005081:Exercise Therapy / Q000379:methods; D005919:Glomerular Filtration Rate; D053612:Janus Kinases / Q000378:metabolism*; D007668:Kidney / Q000503:physiopathology; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D012420:Running; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000201:enzymology / Q000473:pathology; D013550:Swimming; D013997:Time Factors
D015415:Biomarkers; D016207:Cytokines; C494201:Il6st protein, rat; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D050822:Cytokine Receptor gp130; C092073:cardiotrophin 1; D053612:Janus Kinases