Abstract: FR-OR107
Myokines Mediate Muscle-Kidney Crosstalk Suppressing Metabolic Reprogramming and Fibrosis in Damaged Kidneys
Session Information
- Stress Signaling and Fibrosis
November 03, 2017 | Location: Room 277, Morial Convention Center
Abstract Time: 04:54 PM - 05:06 PM
Category: Cell Biology
- 204 Extracellular Matrix Biology, Fibrosis, Cell Adhesion
Authors
- Peng, Hui, The third affiliated hospital of Sun Yat-sen University, Guangzhou, China
- Wang, Yanlin, Baylor College of Medicine, Houston, Texas, United States
- Mitch, William E., Baylor College of Medicine, Houston, Texas, United States
- Thomas, Sandhya S., None, Houston, Texas, United States
- Hu, Zhaoyong, Baylor College of Medicine, Houston, Texas, United States
Background
Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Because exercise might benefit the outcomes of CKD, we hypothesized that the induction of myokines will improve kidney energy metabolism and suppress kidney damage.
Methods
we investigated how a substitute for exercise, overexpression of PGC-1α only in skeletal muscles (mPGC-1a), affects recovery from kidney tubule cell damage in three mouse models including folic acid nephropathy (FAN); unilateral ureteral obstruction (UUO); or subtotal nephrectomy (CKD).
Results
Despite injury from folic acid, unilateral ureteral ligation or subtotal nephrectomy, kidney tubules from mPGC-1α mice resisted progressive cellular damage and subsequent fibrogenesis. Metabolomics analysis revealed improved energy metabolism and ATP production in injured kidneys from mPGC-1α mice. A myokine-enriched serum fraction from mPGC-1α mice (<50 kDa but > 10 kDa) improved energy metabolism in primary cultures of tubule cells. Specifically, the myokine, irisin, protected kidney cells from injury by suppressing metabolic reprogramming. A neutralizing anti-irisin antibody blocked improvements in kidney cell metabolism engendered by serum from mPGC-1a mice. Recombinant irisin administration to mice with kidney injury attenuated kidney damage and fibrosis. The mechanism underlying irisin-initiated improvements is that irisin competes with TGF-β1 for binding to the TGF-b type 2 receptor, thereby impeding activation of the TGF-β type 1 receptor and Smad2/3 signaling, as result, suppression of metabolic reprogramming and fibrogenesis.
Conclusion
myokine-mediated crosstalk between muscle and kidney can protect kidney tubule cell from damage. Myokine, irisin counteracts metabolic reprogramming in injured kidney cells with improvement in kidney function and suppression of kidney fibrosis.
Funding
- Other NIH Support