Katagiri Fumihiko, Ueo Daisuke, Okubo-Gunge Yumi, Usui Aya, Kuwatsuka Sayaka, Mine Yoshiko, Hamada Keisuke, Fujiwara Sakuhei, Sasaki Takako, Nomizu Motoyoshi, Utani Atsushi
Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Department of Dermatology, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
JID Innov. 2022 Mar 9;2(3):100114. doi: 10.1016/j.xjidi.2022.100114. eCollection 2022 May.
Keratins are the major amyloid fibril component in localized cutaneous amyloidosis. We analyzed the amyloid components in the skin of patients with localized cutaneous amyloidosis by immunohistochemical staining using antisera against extracellular matrix proteins and keratin 5 (K5). Fibulin-4 and K5 colocalized in the amyloid deposits. Using 14 synthetic peptides, we screened for amyloidogenic sequences in the C-terminal region of K5, including the α-helical rod domain and the tail domain. Two peptides stained with thioflavin T possessed a β-sheet structure and formed amyloid-like fibrils. Among the amyloidogenic peptides, a peptide KT5-6 (YQELMNTKLALDVEIATYRKLLEGE) derived from the α-helical rod domain of K5 specifically bound to fibulin-4. In addition, amyloid formation of KT5-6 was accelerated by fibulin-4. These results suggest that degraded fragments of K5 containing the KT5-6 sequence form amyloid fibrils with fibulin-4. The data further suggest that degraded fragments of K5 and fibulin-4 have the potential to initiate cutaneous amyloidosis.
角蛋白是局限性皮肤淀粉样变中主要的淀粉样纤维成分。我们通过使用针对细胞外基质蛋白和角蛋白5（K5）的抗血清进行免疫组织化学染色，分析了局限性皮肤淀粉样变患者皮肤中的淀粉样成分。纤连蛋白-4和K5在淀粉样沉积物中共定位。我们使用14种合成肽，在K5的C末端区域筛选淀粉样生成序列，包括α螺旋杆结构域和尾部结构域。两种用硫黄素T染色的肽具有β折叠结构并形成淀粉样纤维。在淀粉样生成肽中，一种源自K5的α螺旋杆结构域的肽KT5-6（YQELMNTKLALDVEIATYRKLLEGE）特异性结合纤连蛋白-4。此外，纤连蛋白-4加速了KT5-6的淀粉样形成。这些结果表明，含有KT5-6序列的K5降解片段与纤连蛋白-4形成淀粉样纤维。数据进一步表明，K5和纤连蛋白-4的降解片段有可能引发皮肤淀粉样变。
