C1q level, a surrogate or prediction marker?

Short summary of Cho KJ et al; Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q. Sci Rep 2016, 6: 18840

Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been hypothesized to participate in the pathology of neurodegenerative diseases. The systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of selective striatal lesions.

Recently, it has been proposed that complement-mediated synapse elimination may be reactivated aberrantly in the pathology of neurodegenerative diseases.

ASK1 may be involved in regulation of astrocyte TGF-beta and it is linked to the C1q level in spatial and temporal, and moreover in the earlier stage of progressing striatal neuronal loss. Conclusively the present study suggests that ASK1 mediates 3-NP toxicity and regulates C1q level through the astrocyte TGF-beta. It may also suggest that C1q level may be a surrogate of prediction marker representing neurodegenerative disease progress before developing behavioral impairment.

The infusion of 3-NP leads to selective striatal neuronal loss as well as astrocyte reactivation. Results from 3-NP-infused mouse blood serum revealed that the secretion levels of C1q were increased on day four when the lesion was not yet detectable and on day seven when the lesion was detectable in 3-NP infused mice.


C1q promotes arterial remodeling

Short summary of Yabumoto C et al; Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression. Sci Rep 2015, 5: 14453

Down-regulation of the aging-promoting C1q mediated beneficial effects of AT1 receptor blockade on muscle repair and regeneration. We recently identified C1q as a diffusible factor in the serum that activates canonical Wnt/β -catenin signaling by binding to Wnt receptor Frizzled and by inducing cleavage of Wnt coreceptor LRP618. Serum and tissue concentrations of C1q showed a significant increase with aging, and C1q-mediated activation of Wnt/β -catenin signaling led to aging-related decline in regeneration capacity of skeletal muscles. C1q treatment attenuated satellite cell proliferation and stimulated fibroblast proliferation both in vitro and in vivo. We also reported that M2 macrophages were recruited to the aorta and secreted C1q, which promoted arterial remodeling through activation of Wnt/β -catenin signaling, in Ang II-infused mice.

We propose that AT1 receptor blockade reduces systemic and local levels of C1q through inhibiting C1q production by infiltrated macrophages, and thereby enhances activation and proliferation of satellite cells. Insomuch as AT1 receptor is expressed in both myocytes and macrophages, further studies will be required to elucidate the cell type-specific role of AT1 receptor in inducing C1q expression in macrophages in injured muscles.


Serum C1q concentrations in mice treated with irbesartan or vehicle at 4 days after cryoinjury or sham operation (n = 12, in each group). Data are presented as mean ± SEM. *P < 0.05. NS, not significant.