Di Girolamo Nick, Sarris Maria, Chui Jeanie, Cheema Haroon, Coroneo Minas T, Wakefield Denis
Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, and Department of Ophthalmology, Prince of Wales Hospital, Sydney, NSW, Australia.
J Cell Mol Med. 2008 Dec;12(6B):2799-811. doi: 10.1111/j.1582-4934.2008.00290.x.
Biological effects of nerve growth factor (NGF) are mediated through receptors known as nerve growth factor receptors (NGFR), which include p75 and TrkA. This study was initiated after identifying NGFR as an up-regulated gene in the limbus by cDNA microarray analysis and we postulate that its expression may be indicative of a stem/progenitor cell phenotype. Immunohistochemistry was performed on normal human adult (n=5) and foetal (n=3) corneal tissue using antibodies directed against p75, TrkA, NGF, p63, ABCG2 and CK3/12. Limbal, conjunctival and pterygium tissue was obtained from patients (n=10) undergoing pterygium resection and used for immunohistochemical assessment. Paraffin-embedded archival human skin specimens (n=4) were also evaluated. In vitro expression of NGFR was determined in limbal, conjunctival and pterygium-derived epithelial cells. p75 was selectively expressed by basal epithelial cells in pterygia, conjunctiva and limbus, but was absent in the central cornea. These results were confirmed with two additional p75 specific antibodies. In contrast, TrkA was found in full-thickness pterygium, conjunctival, limbal and corneal epithelium in both adult and foetal eyes. p75 expression was identified in a small percentage, while TrkA was found on the entire population of cultured conjunctival, limbal and pterygium-derived epithelial cells. This receptor was also observed in selective regions of the human epidermis and hair follicle bulge. Our results illustrate the selective expression of p75 in basal pterygium, conjunctival and limbal epithelium, while staining was absent in adult and foetal central cornea. p75 may represent an additional ocular surface epithelial stem/progenitor cell signature gene.
神经生长因子（NGF）的生物学效应是通过被称为神经生长因子受体（NGFR）的受体介导的，其中包括p75和TrkA。本研究是在通过cDNA微阵列分析将NGFR鉴定为角膜缘中上调的基因后启动的，我们推测其表达可能指示干细胞/祖细胞表型。使用针对p75、TrkA、NGF、p63、ABCG2和CK3/12的抗体，对正常成人（n=5）和胎儿（n=3）角膜组织进行了免疫组织化学分析。从接受翼状胬肉切除术的患者（n=10）获取翼状胬肉、结膜和翼状胬肉组织，并用于免疫组织化学评估。还评估了石蜡包埋的存档人类皮肤标本（n=4）。测定了翼状胬肉、结膜和翼状胬肉来源的上皮细胞中NGFR的体外表达。p75在翼状胬肉、结膜和角膜缘的基底上皮细胞中选择性表达，但在中央角膜中不存在。用另外两种p75特异性抗体证实了这些结果。相比之下，在成人和胎儿眼睛的全层翼状胬肉、结膜、角膜缘和角膜上皮中均发现了TrkA。在一小部分细胞中鉴定出p75表达，而在培养的结膜、角膜缘和翼状胬肉来源的上皮细胞群体中均发现了TrkA。在人类表皮和毛囊隆突的选择性区域也观察到了这种受体。我们的结果表明，p75在翼状胬肉、结膜和角膜缘基底上皮中选择性表达，而在成人和胎儿中央角膜中无染色。p75可能代表另一种眼表上皮干细胞/祖细胞特征基因。
