Abstract 9518: Follistatin-like 1 Functions as a Cardiokine That Plays a Protective Role in Renal Injury

Abstract

Objective: Heart diseases including chronic heart failure contribute to the progression of chronic kidney disease. Heart tissue produces a variety of secretory proteins, also known as cardiokines, which play roles in inter-cellular and inter-tissue communication under physiological and pathological conditions. Recently we found that follistatin-like 1 (Fstl1) acts as a stress-inducible cardiokine that exerts cardio-protective function. Here, we investigated the role of cardiac Fstl1 in renal disease in a mouse model of subtotal nephrectomy. Methods and Results: Cardiac specific Fstl1-deficient (Fstl1-KO) mice were generated by crossing cardiac myocyte-specific α-MHC-Cre transgenic mice and Fstl1 flox/flox mice. Subtotal (5/6) nephrectomy operation was performed in Fstl1-KO mice and control mice. At 2 months after operation, urinary albumin excretion was significantly increased in Fstl1-KO mice compared to control mice. A histological analysis of the remnant kidney demonstrated that Fstl1-KO mice showed a significant increase in intraglomerular cell number and glomerular size compared to control mice. Fstl1-KO mice also had a larger area of tubulointerstitial fibrosis in the remnant kidney compared to control mice, which was accompanied with increased mRNA levels of transforming growth factor-β1 and collagen type I/III. Furthermore, Fstl1-KO mice showed elevated expression levels of NADPH oxidase components and pro-inflammatory cytokines including TNF and IL-6 in the remnant kidney. Conclusions: Our findings indicate that Fstl1 functions as a cardiokine that prevents glomerular and tubulointerstitial damages through attenuation of oxidative stress and inflammatory response.