| Literature DB >> 22682250 |
Atsuhiko T Naito1, Tomokazu Sumida, Seitaro Nomura, Mei-Lan Liu, Tomoaki Higo, Akito Nakagawa, Katsuki Okada, Taku Sakai, Akihito Hashimoto, Yurina Hara, Ippei Shimizu, Weidong Zhu, Haruhiro Toko, Akemi Katada, Hiroshi Akazawa, Toru Oka, Jong-Kook Lee, Tohru Minamino, Toshio Nagai, Kenneth Walsh, Akira Kikuchi, Misako Matsumoto, Marina Botto, Ichiro Shiojima, Issei Komuro.
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.Entities:
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Year: 2012 PMID： 22682250 PMCID： PMC3529917 DOI： 10.1016/j.cell.2012.03.047
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582