Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes

被引：260

作者：

Naito, Atsuhiko T. ^{[1
,3
]}

Sumida, Tomokazu ^{[4
]}

Nomura, Seitaro ^{[4
]}

Liu, Mei-Lan ^{[4
]}

Higo, Tomoaki ^{[1
]}

Nakagawa, Akito ^{[1
]}

Okada, Katsuki ^{[1
]}

Sakai, Taku ^{[1
]}

Hashimoto, Akihito ^{[1
]}

Hara, Yurina ^{[1
]}

Shimizu, Ippei ^{[4
]}

Zhu, Weidong ^{[4
]}

Toko, Haruhiro ^{[4
]}

Katada, Akemi ^{[4
]}

Akazawa, Hiroshi ^{[1
,3
]}

Oka, Toru ^{[1
,3
]}

Lee, Jong-Kook ^{[1
,3
]}

Minamino, Tohru ^{[4
]}

Nagai, Toshio ^{[4
]}

Walsh, Kenneth ^{[5
]}

Kikuchi, Akira ^{[2
]}

Matsumoto, Misako ^{[6
]}

Botto, Marina ^{[7
]}

Shiojima, Ichiro ^{[1
,3
]}

Komuro, Issei ^{[1
,3
,4
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Mol Biol & Biochem, Osaka 5650871, Japan

[3] Japan Sci & Technol Agcy, CREST, Tokyo 1020075, Japan

[4] Chiba Univ, Grad Sch Med, Dept Cardiovasc Sci & Med, Chiba 2608670, Japan

[5] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA

[6] Hokkaido Univ, Grad Sch Med, Dept Microbiol & Immunol, Sapporo, Hokkaido 0608638, Japan

[7] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Complement & Inflammat Res, London SW7 2AZ, England

来源：

CELL | 2012年 / 149卷 / 06期

基金：

日本科学技术振兴机构;

关键词：

1ST COMPONENT; BETA-CATENIN; MECHANISM; RECEPTOR; PATHWAY; CELLS; SUBCOMPONENT; INHIBITION; PROTEINS; IMMUNITY;

D O I：

10.1016/j.cell.2012.03.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

\ 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.

引用

页码：1298 / 1313

页数：16

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