FOLLISTATIN MODULATES ISCHAEMIA-REPERFUSION-INDUCED RENAL FIBROSIS IN MICE

D FANG1,2, B LU1, S HAYWARD3 D DE KRETSER3,4, P COWAN1,2, K DWYER2

1Immunology Research Centre, St. Vincent’s Hospital Melbourne, Victoria; 2Department of Medicine, the University of Melbourne, Victoria; 3Hudson Institute of Medical Research, Victoria; 4Monash University, Clayton, Victoria

Aim: To examine the therapeutic potential of follistatin in renal fibrosis.

Background: Activin and its binding protein, follistatin, play critical roles in the regulation of inflammation and fibrosis. Activins are upregulated in ischaemia-reperfusion injury (IRI). Injection of a viral vector carrying the follistatin gene (rAAV-FS) results in sustained elevation of circulating follistatin in mice and attenuates ischaemia-reperfusion-induced acute kidney injury.

Methods: 2 groups of mice underwent renal IRI surgery. Group 1 had rAAV-FS or empty-vector (control) injected 4 weeks before IRI (to ensure elevated follistatin levels at the time of injury). Group 2 had the vectors injected immediately before IRI (i.e. normal follistatin levels at the time of injury, but increasing thereafter). Mice were sacrificed 4 weeks post-reperfusion. Serum activin, follistatin and creatinine, Masson’s stained kidney sections and pro-fibrotic markers were assessed.

Results: Four weeks post-IRI, control mice had increased expression of pro-fibrotic markers (TGFβ-1, p<0.01; connective tissue growth factor (CTGF), p<0.05; collagen I, p<0.01; collagen IV, p<0.01), renal fibrosis (p<0.01), and serum creatinine (p<0.01). Compared to control mice, rAAV-FS treated IRI mice had 6-fold increase in circulating follistatin levels (p<0.0001) with associated reductions in activin A and B (p<0.001). rAAV-FS treated IRI mice in group 1 had significant reduction in expression of pro-fibrotic markers (TGFβ-1, p<0.05; CTGF, p<0.05; collagen I, p<0.01; collagen IV, p=0.05), renal fibrosis (p<0.01), and serum creatinine (p<0.05). However, rAAV-FS treated IRI mice in group 2 did not have statistically significant reduction in pro-fibrotic markers, renal fibrosis (p=0.06) and serum creatinine.

Conclusions: Elevated follistatin around IRI seems crucial to protect against renal fibrosis development. These data suggest early post-IRI may be the key period that follistatin acts to modulate renal fibrosis.

About ANZSN

The ASM is hosted by Australian and New Zealand Society of Nephrology.

The aims of the Society are to promote and support the study of the kidney and urinary tract in health and disease, and to ensure the highest professional standards for the practice of nephrology in Australia and New Zealand.

Conference Managers

Please contact the team at Conference Design with any questions regarding the Annual Scientific Meeting

/wp-content/uploads/2017/08/Conference-Design-400×400.png

© 2015 - 2016 Conference Design Pty Ltd