Li D Q, Tseng S C
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Florida 33101.
J Cell Physiol. 1995 Apr;163(1):61-79. doi: 10.1002/jcp.1041630108.
Signals transmitted from mesenchyme to epithelia or vice versa constitute the basis of reciprocal epithelial-mesenchymal interactions. As a first step toward understanding epithelial-mesenchymal interactions on the ocular surface where the transit amplifying cell-containing corneal epithelium is anatomically separated from the stem cell-containing limbal epithelium, we sought to characterize the expression patterns of cytokines and their receptors by primary epithelial and early-passaged fibroblast cultures of human cornea and limbus. Northern hybridization with oligonucleotide and cDNA probes to a total of 25 cytokines and 12 of their receptors revealed that the positively expressed cytokines could be divided into the following four patterns. Type I: TGF-alpha, IL-1 beta, and PDGF-B were expressed exclusively by epithelial cells but their respective receptors EGFR and IL-1R were predominantly and PDGFR-beta was exclusively expressed by fibroblasts. Type II: IGF-I, TGF-beta 1, -beta 2, LIF, and bFGF, and their receptors were expressed by both epithelial cells and fibroblasts. FGFR-1 (flg) and FGFR-2 (bek) were expressed more by fibroblasts and bFGF was expressed more by corneal than limbal epithelial cells. Type III: keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) were expressed exclusively by fibroblasts and their respective receptors, KGFR and c-met, were predominantly expressed by epithelial cells. Combined with RT-PCR, the quantity of KGF and KGFR transcripts was highest in limbal fibroblasts and epithelial cells, respectively. In contrast, the quantity of HGF and HGFR (c-met) transcripts was highest in corneal fibroblasts and epithelial cells, respectively. Type IV: M-CSF and IL-8 were expressed by fibroblasts and/or epithelial cells but their receptors were not expressed by epithelial cells nor fibroblasts, but by immune or inflammatory cells. In addition to these potential paracrine actions, autocrine actions mediated by TGF-alpha/EGFR, IL-1 beta/IL1-R, and bFGF/FGFR-1 were more expressed by corneal than limbal epithelial cells. Immunofluorescence staining on human corneoscleral cryosections confirmed that EGFR and bFGF were not expressed by the limbal basal epithelium, but expressed strongly by the corneal epithelium, a pattern consistent with Northern hybridization. These results indicate that ocular surface epithelial cells and fibroblasts can express a myriad of cytokines, among which the first three patterns constitute the network of potential epithelial-mesenchymal cytokine dialogues. The difference of certain cytokine expression between corneal and limbal regions suggests that this network participates in normal epithelial growth and differentiation, and plays an important role in wound healing.
从间充质传递至上皮或反之的信号构成了上皮 - 间充质相互作用的基础。作为理解眼表上皮 - 间充质相互作用的第一步，在眼表，含过渡增殖细胞的角膜上皮在解剖学上与含干细胞的角膜缘上皮分离，我们试图通过人角膜和角膜缘的原代上皮细胞及早期传代的成纤维细胞培养来表征细胞因子及其受体的表达模式。用寡核苷酸和cDNA探针与总共25种细胞因子及其12种受体进行Northern杂交，结果显示阳性表达的细胞因子可分为以下四种模式。模式I：TGF-α、IL-1β和PDGF-B仅由上皮细胞表达，但其各自的受体EGFR和IL-1R主要由成纤维细胞表达，而PDGFR-β仅由成纤维细胞表达。模式II：IGF-I、TGF-β1、-β2、LIF和bFGF及其受体在上皮细胞和成纤维细胞中均有表达。FGFR-1（flg）和成纤维细胞表达较多，bFGF在角膜上皮细胞中的表达多于角膜缘上皮细胞。模式III：角质形成细胞生长因子（KGF）和肝细胞生长因子（HGF）仅由成纤维细胞表达，其各自的受体KGFR和c-met主要由上皮细胞表达。结合RT-PCR，KGF和KGFR转录本的量分别在角膜缘成纤维细胞和上皮细胞中最高。相反，HGF和HGFR（c-met）转录本的量分别在角膜成纤维细胞和上皮细胞中最高。模式IV：M-CSF和IL-8由成纤维细胞和/或上皮细胞表达，但其受体既不由上皮细胞也不由成纤维细胞表达，而是由免疫或炎症细胞表达。除了这些潜在的旁分泌作用外，由TGF-α/EGFR、IL-1β/IL1-R和bFGF/FGFR-1介导的自分泌作用在角膜上皮细胞中的表达多于角膜缘上皮细胞。人角膜巩膜冰冻切片的免疫荧光染色证实，EGFR和bFGF在角膜缘基底上皮中不表达，但在角膜上皮中强烈表达，这一模式与Northern杂交一致。这些结果表明，眼表上皮细胞和成纤维细胞可表达多种细胞因子，其中前三种模式构成了潜在的上皮 - 间充质细胞因子对话网络。角膜和角膜缘区域某些细胞因子表达的差异表明，该网络参与正常上皮生长和分化，并在伤口愈合中起重要作用。
