Fibulin-5 is a novel substrate for granzyme B, its degradation causes dysfunction of elastic fiber assembly by ultraviolet irradiation.

Summary: Abstract Body: Fibulin-5, an elastin-binding extracellular matrix (ECM) protein acts as an essential factor for elastic fiber assembly. The absence of fibulin-5 alters structure and assembly of elastic fibers, causing a reduction in skin extensibility and elasticity. Granzyme B (GrB), a serine protease, elevated by ultraviolet (UV) irradiation, etc., degrades dermal ECMs and is involved in structural remodeling in the dermis. Structure of elastic fibers is impaired by chronic UV exposure, which not only causes the degradation but also fails the remodeling process of elastic fibers, while the detailed mechanism is not clear. In this study, we identified that fibulin-5 is a novel substrate for GrB. Fibulin-5 fragments cleaved by GrB could not bind tropoelastin and thus failed to assemble elastic fibers. Furthermore, we investigated that UVB irradiation in keratinocytes increases GrB and disrupts fiburin-5 and elastic fibers. The disruptions were rescued by GrB inhibition. These results suggest that the cleavage of fibulin-5 by GrB is likely involved in the dysfunction of elastic fiber assembly by UV exposure. Hiroko Yamasaki¹, Misato Yamano¹, Hirotsugu Kamei¹, Eri Kondoh¹ 1. Shinagawa Research and Development Center, Sato Pharmaceutical Co., Ltd., Tokyo, Japan. Epidermal Structure and Barrier Function