An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis

Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology. First, we examined lamellar tissue from healthy Standardbred horses and those with induced hyperinsulinemia and laminitis for EGFR distribution and quantity using immunostaining and gene expression, respectively. Phosphorylation of EGFR was also quantified. Next, plasma EGF concentrations were compared in healthy and insulin-infused horses, and in healthy and insulin-dysregulated ponies before and after feeding. The EGFR were localised to the secondary epidermal lamellae, with stronger staining in parabasal, rather than basal, cells. No change in EGFR gene expression occurred with laminitis, although the receptor showed some phosphorylation. No difference was seen in EGF concentrations in horses, but in insulin-dysregulated ponies mean, post-prandial EGF concentrations were almost three times higher than in healthy ponies (274 ± 90 vs. 97.4 ± 20.9 pg/mL, P = 0.05). Although the EGFR does not appear to play a major pathogenic role in hyperinsulinemic laminitis, the significance of increased EGF in insulin-dysregulated ponies deserves further investigation.

马蹄叶炎（Equine laminitis）是一种以表皮细胞增殖与结构崩解为典型特征的指（趾）表皮层板（digital epidermal lamellae）疾病。该病最常见的诱因为高胰岛素血症（hyperinsulinemia），但其发病机制尚未完全阐明。胰岛素可在其他物种中激活表皮生长因子（epidermal growth factor, EGF）系统，本研究验证了"表皮生长因子受体（epidermal growth factor receptor, EGFR）信号通路上调是马蹄叶炎病理生理学关键驱动因素"这一假说。
首先，我们分别采用免疫染色与基因表达技术，对健康美国标准马以及诱导罹患高胰岛素血症与蹄叶炎的马的层板组织中EGFR的分布与表达水平进行了检测，并定量分析了EGFR的磷酸化水平。
随后，我们对比了健康马与胰岛素输注马的血浆EGF浓度，同时分析了健康矮马与胰岛素调节异常矮马在饲喂前后的血浆EGF浓度变化。EGFR定位于次级表皮层板，且在副基底层细胞中的染色信号强于基底层细胞。尽管该受体存在一定程度的磷酸化，但蹄叶炎状态下EGFR的基因表达未出现显著变化。马的血浆EGF浓度未出现明显差异，但在胰岛素调节异常的矮马中，餐后平均EGF浓度几乎为健康矮马的3倍（274 ± 90 vs. 97.4 ± 20.9 pg/mL，P = 0.05）。
尽管EGFR似乎并未在高胰岛素血症性蹄叶炎中发挥主要致病作用，但胰岛素调节异常矮马体内EGF水平升高的生物学意义仍有待进一步研究。