Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 26, Issue 3, Pages 636-646Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2014020210
Keywords
-
Categories
Funding
- Takeda Science Foundation
- Uehara Memorial Foundation
- Daiichi-Sankyo Foundation of Life Science
- SENSHIN Medical Research Foundation
- Cardiovascular Research Fund, Tokyo, Japan
- Grants-in-Aid for Scientific Research [25461105] Funding Source: KAKEN
Ask authors/readers for more resources
Heart disease contributes to the progression of CKD. Heart tissue produces a number of secreted proteins, also known as cardiokines, which participate in intercellular and intertissue communication. We recently reported that follistatin-like 1 (Fstl1) functions as a cardiokine with cardioprotective properties. Here, we investigated the role of cardiac Fstl1 in renal injury after subtotal nephrectomy. Cardiac-specific Fstl1-deficient (cFstl1-KO) mice and wild-type mice were subjected to subtotal (5/6) nephrectonny. cFstl1-KO mice showed exacerbation of urinary albumin excretion, glonnerular hypertrophy, and tubulointerstitial fibrosis after subtotal renal ablation compared with wild-type mice. cFstl1-KO mice also exhibited increased mRNA levels of proinflammatory cytokines, including TNF-alpha and IL-6, NADPH oxidase components, and fibrotic mediators, in the remnant kidney. Conversely, systemic administration of adenoviral vectors expressing Fstl1 (Ad-Fstl1) to wild-type mice with subtotal nephrectonny led to amelioration of albuminuria, glomerular hypertrophy, and tubulointerstitial fibrosis, accompanied by reduced expression of proinflammatory mediators, NADPH oxidase components, and fibrotic markers in the remnant kidney. In cultured human mesangial cells, treatment with recombinant FSTL1 attenuated TNF-alpha-stimulated expression of proinflammatory cytokines. Treatment of mesangial cells with FSTL1 augmented the phosphorylation of AMP-activated protein kinase (AMPK), and inhibition of AMPK activation abrogated the anti-inflammatory effects of FSTL1. These data suggest that Fstl1 functions in cardiorenal communication and that the lack of Fstl1 production by myocytes promotes glonnerular and tubulointerstitial damage in the kidney.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available