Abstract 12866: Complement C1q is an Activator of Wnt Signaling Involved in Mammalian Aging and in Pathogenesis of Heart Failure
The Wnt signaling pathway plays critical roles in development and diseases. It was previously reported that activation of canonical Wnt signaling by a substance in the serum is involved in mammalian aging and aging-related impairment in tissue regeneration. Here, we report that complement C1q is an activator of canonical Wnt signaling in the serum. Serum C1q concentration was increased with aging, and C1q activated canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt co-receptor low-density-lipoprotein receptor-related protein 6. The regenerative capacity of skeletal muscle in young mice was reduced by C1q treatment, whereas aging-associated impairment in muscle regeneration was restored by C1s blockade. In C1qa-deficient mice, downregulation of canonical Wnt signaling was observed in various tissues, most notably in spleen and lymph nodes. We have also found that serum C1q level is increased in mice with heart failure and elevation of serum C1q level was associated with activation of Wnt signaling in the heart. Inhibition of C1q-induced Wnt signaling partially prevented the progression into heart failure after pressure overload. Collectively, our findings implicate that C1q-induced Wnt signaling is involved in mammalian aging and in various diseases including heart failure.
- © 2010 by American Heart Association, Inc.