Atabai K, Jame S, Azhar N et al.Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J Clin Invest 119:3713-3722

Lung Biology Center, Cardiovascular Research Institute, UCSF, San Francisco, California, USA.
The Journal of clinical investigation (Impact Factor: 13.22). 11/2009; 119(12):3713-22. DOI: 10.1172/JCI40053
Source: PubMed


Milk fat globule epidermal growth factor 8 (Mfge8) is a soluble glycoprotein known to regulate inflammation and immunity by mediating apoptotic cell clearance. Since fibrosis can occur as a result of exaggerated apoptosis and inflammation, we set out to investigate the hypothesis that Mfge8 might negatively regulate tissue fibrosis. We report here that Mfge8 does decrease the severity of tissue fibrosis in a mouse model of pulmonary fibrosis; however, it does so not through effects on inflammation and apoptotic cell clearance, but by binding and targeting collagen for cellular uptake through its discoidin domains. Initial analysis revealed that Mfge8-/- mice exhibited enhanced pulmonary fibrosis after bleomycin-induced lung injury. However, they did not have increased inflammation or impaired apoptotic cell clearance after lung injury compared with Mfge8+/+ mice; rather, they had a defect in collagen turnover. Further experiments indicated that Mfge8 directly bound collagen and that Mfge8-/- macrophages exhibited defective collagen uptake that could be rescued by recombinant Mfge8 containing at least one discoidin domain. These data demonstrate a critical role for Mfge8 in decreasing the severity of murine tissue fibrosis by facilitating the removal of accumulated collagen.

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Available from: Paul J Wolters, Dec 09, 2014
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    • "This correlates well with findings that uptake of ECM components appears to be mediated by M2 macrophages. Uptake of these components is mediated by different mannose receptors [27] and by glycoprotein milk fat globule epidermal growth factor 8 (Mfge8) [219]. Mannose receptors of course are a known M2 marker, and for Mfge8 this is unclear. "
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