Journal article

Activin A-Induced Cachectic Wasting Is Attenuated by Systemic Delivery of Its Cognate Propeptide in Male Mice

Kelly L Walton, Justin L Chen, Quinn Arnold, Emily Kelly, Mylinh La, Louis Lu, George Lovrecz, Adam Hagg, Timothy D Colgan, Hongwei Qian, Paul Gregorevic, Craig A Harrison



In cancer, elevated activin levels promote cachectic wasting of muscle, irrespective of tumor progression. In excess, activins A and B use the myostatin signaling pathway in muscle, triggering a decrease in protein synthesis and an increase in protein degradation, which ultimately leads to atrophy. Recently, we demonstrated that local delivery of engineered activin and myostatin propeptides (natural inhibitors of these growth factors) could induce profound muscle hypertrophy in healthy mice. Additionally, the expression of these propeptides effectively attenuated localized muscle wasting in models of dystrophy and cancer cachexia. In this study, we examined whether a systemically administere..

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Awarded by National Health and Medical Research Council (NHMRC) Australia

Funding Acknowledgements

Support for this work was provided by Project Grant and Fellowship funding [no. 1078907 (to P.G. and C.A.H.) and no. 1046782 (to P.G.)] from the National Health and Medical Research Council (NHMRC) Australia. J.L.C. was supported by a postdoctoral fellowship from the Cancer Council Victoria. An Early Career Seed Grant from the Victorian Cancer Agency supported K.L.W. The Hudson Institute of Medical Research and Baker Heart and Diabetes Institute are supported, in part, by the Operational Infrastructure Support Program of the Victorian Government.