Martano Manuela, Altamura Gennaro, Power Karen, Liguori Pierluigi, Restucci Brunella, Borzacchiello Giuseppe, Maiolino Paola
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
DVM, EQUINE CLINIC Punto Verde, 81110 Caserta, Italy.
Animals (Basel). 2021 Dec 23;12(1):20. doi: 10.3390/ani12010020.
It is well known that δ-bovine papillomaviruses (BPV-1, BPV-2 and BPV-13) are one of the major causative agents of equine sarcoids, the most common equine skin tumors. Different viruses, including papillomaviruses, evolved ingenious strategies to modulate autophagy, a complex process involved in degradation and recycling of old and damaged material.
The aim of this study was to evaluate, by immunohistochemistry (IHC) and Western blot (WB) analysis, the expression of the main related autophagy proteins (Beclin 1, protein light chain 3 (LC3) and P62), in 35 BPV1/2 positive equine sarcoids and 5 BPV negative normal skin samples.
Sarcoid samples showed from strong-to-moderate cytoplasmic immunostaining, respectively, for Beclin 1 and P62 in >60% of neoplastic fibroblasts, while LC3 immunostaining was weak to moderate in ≤60% of neoplastic fibroblasts. Western blot analysis confirmed the specificity of the antibodies and revealed no activation of autophagic flux despite Beclin 1 overexpression in sarcoid samples.
Results could suggest the activation of the initial phase of autophagy in equine sarcoids, and its impairment during the following steps. The impairment of autophagy could lead to a selection of a quiescent population of fibroblasts, which survive longer in a hypoxic microenvironment and produced more and/or altered collagen.
众所周知，δ-牛乳头瘤病毒（BPV-1、BPV-2和BPV-13）是马属肉瘤的主要致病因子之一，马属肉瘤是马最常见的皮肤肿瘤。包括乳头瘤病毒在内的不同病毒，进化出了巧妙的策略来调节自噬，自噬是一个涉及旧的和受损物质降解与再循环的复杂过程。
本研究旨在通过免疫组织化学（IHC）和蛋白质印迹（WB）分析，评估35个BPV1/2阳性马属肉瘤和5个BPV阴性正常皮肤样本中主要相关自噬蛋白（Beclin 1、微管相关蛋白1轻链3（LC3）和P62）的表达。
在超过60%的肿瘤性成纤维细胞中，肉瘤样本中Beclin 1和P62分别显示出从强到中度的细胞质免疫染色，而在≤60%的肿瘤性成纤维细胞中，LC3免疫染色为弱到中度。蛋白质印迹分析证实了抗体的特异性，并显示尽管肉瘤样本中Beclin 1过表达，但自噬流未被激活。
结果可能提示马属肉瘤中自噬初始阶段被激活，而在随后的步骤中受到损害。自噬受损可能导致选择一群静止的成纤维细胞，它们在缺氧微环境中存活时间更长，并产生更多和/或改变的胶原蛋白。
