ABSTRACT
Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice, but not in those of C1qa-deficient mice. C1q activates canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt coreceptor low-density lipoprotein receptor-related protein 6. Skeletal muscle regeneration in young mice is inhibited by exogenous C1q treatment, whereas aging-associated impairment of muscle regeneration is restored by C1s inhibition or C1qa gene disruption. Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging.
Subject(s)
Aging/metabolism , Complement C1q/metabolism , Wnt Signaling Pathway , Animals , Complement C1s/metabolism , Humans , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Mice , Serum/metabolismABSTRACT
There have been great progresses in our knowledge of patho-physiology on various cardiovascular diseases, which enabled us to develop the field of regenerative medicine for previously untreatable patients. Among several strategies in cardiovascular regenerative medicine, cell transplantation is one of the best studied and the best clinically practiced. In this review we will first summarize the mechanisms of cell therapy, and then go through lists of cells and diseases that can be applied. Later we will introduce some of the clinical experiences published so far, with some discussion regarding the problems and perspectives of this novel therapeutics.
