The roles of α2AP in the pathogenesis of systemic sclerosis

Systemic sclerosis (SSc) is autoimmune rheumatic disease of unknown etiology that is characterized by the fibrosis of skin and visceral organs, and peripheral circulatory disturbance.

Fig. 1. (A) α2AP induces pro-fibrotic changes. (B) The α2AP neutralization attenuates pro-fibrotic changes in SSc.

In our study, we found that alpha2-antiplasmin (α2AP), which is known to the principal inhibitor of plasmin, induced pro-fibrotic changes, such as increased collagen production, and myofibroblast differentiation in mice and human dermal fibroblasts (Fig. 1 A).  The expression of α2AP was elevated in SSc dermal fibroblasts, and the α2AP neutralization prevented pro-fibrotic changes in SSc dermal fibroblasts and SSc model mice (Fig. 1 B).  Our findings demonstrated that α2AP has a pro-fibrotic effect, and that the blocking of α2AP exerts an anti-fibrotic effect in humans and mice with SSc.

Yosuke Kanno
Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science
Doshisha Women’s Collage of Liberal Arts
Kyoto, Japan

 

Publication

The Antifibrotic Effect of α2AP Neutralization in Systemic Sclerosis Dermal Fibroblasts and Mouse Models of Systemic Sclerosis.
Kanno Y, Shu E, Kanoh H, Seishima M.
J Invest Dermatol. 2016 Apr

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