Keratinic amyloid deposition in canine hair follicle tumors
Keratinic amyloid deposition in canine hair follicle tumors
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DOI：
10.1177/03009858221128924
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发表时间：
2022-10-11
影响因子：
2.4
通讯作者：
Murakami, Tomoaki
中科院分区：
文献类型：
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作者：
Kobayashi, Kyoko;Iwaide, Susumu;Murakami, Tomoaki
角蛋白原发性局限性皮肤淀粉样变性是一种人类疾病；然而，尚未有动物出现类似情况的报道。本研究旨在调查狗的皮肤角蛋白淀粉样蛋白沉积并阐明其病因。对犬毛囊肿瘤组织进行组织病理学分析。进行了基于免疫组织化学和质谱的蛋白质组分析来鉴定候选前体蛋白。进行结构预测和体外纤维化分析以确定淀粉样蛋白生成区域，并进行基因测序分析以评估突变。在 266 个样本中，16 个存在淀粉样蛋白沉积。在肿瘤基质、角蛋白碎片边缘和正常毛囊周围发现了淀粉样蛋白沉积物。细胞角蛋白 5 (CK5) 被确定为候选前体蛋白。在淀粉样蛋白沉积物中观察到 CK5 的 C 端截短，截短位点根据沉积模式而变化。柴犬中淀粉样蛋白沉积的发生率显着较高，并且在这些狗中鉴定出CK5氨基酸多态性。犬和人 CK5 的 C 末端区域的一部分在体外表现出高度淀粉样蛋白生成特性。这项研究揭示了动物体内皮肤角蛋白淀粉样蛋白沉积的存在，并将 CK5 鉴定为淀粉样蛋白前体蛋白，为了解皮肤淀粉样变性的病因学提供了新的见解。
Keratinic primary localized cutaneous amyloidosis is a disease in humans; however, no similar condition has been reported in animals. This study aimed to investigate cutaneous keratinic amyloid deposition in dogs and elucidate its etiology. Canine hair follicle tumor tissues were histopathologically analyzed. Immunohistochemistry and mass spectrometry-based proteomic analyses were performed to identify precursor protein candidates. Structural prediction and in vitro fibrillization analyses were conducted to determine the amyloidogenic region and gene sequencing analysis was performed to assess mutations. Of the 266 samples, 16 had amyloid deposition. Amyloid deposits were found in the stroma of tumors and in the margins of keratin debris and around normal hair follicles. Cytokeratin 5 (CK5) was identified as a precursor protein candidate. C-terminal truncation of CK5 was observed in amyloid deposits, and the truncation sites varied depending on the deposition pattern. There was a significantly higher incidence of amyloid deposition in Shiba dogs, and CK5 amino acid polymorphisms were identified in these dogs. A part of the C-terminal region of both canine and human CK5 exhibited highly amyloidogenic properties in vitro. This study revealed the existence of cutaneous keratinic amyloid deposition in animals and identified CK5 as an amyloid precursor protein, providing novel insights into understanding the etiology of cutaneous amyloidosis.