Department of Ophthalmology and Vision Science, Eye and Ear, Nose, Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
NHC Key Laboratory of Myopia, Fudan University, Shanghai, China.
J Cell Mol Med. 2022 Dec;26(23):5858-5871. doi: 10.1111/jcmm.17609. Epub 2022 Nov 8.
As the main loading-bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell-5000™ tension system. We found that CXC- ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2-STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling.
作为眼睛的主要承重组织，巩膜在青光眼的病理生理学中发挥着重要作用。眼内压（IOP）对巩膜产生机械应变。最近的研究表明，巩膜，特别是视盘周围巩膜，在机械应变下经历复杂的重塑。然而，人眼高血压性巩膜重塑的机制仍不清楚。在这项研究中，应用 Flexcell-5000™张力系统对人眼视盘周围巩膜成纤维细胞（ppHSFs）施加周期性机械应变。我们发现，应变后 CXC-配体和 CXCR2 的表达存在差异。当应变下 CXCR2 上调时，观察到细胞增殖增加和运动性抑制，而当 CXCR2 被敲低时，细胞增殖和运动性没有明显变化。CXCR2 可以通过 JAK1/2-STAT3 信号通路促进细胞增殖能力，调节 I 型胶原和基质金属蛋白酶 2 的 mRNA 和蛋白表达。此外，CXCR2 可能通过 FAK/MLC 途径抑制细胞迁移。总之，CXCR2 调节蛋白的产生并影响 ppHSFs 的细胞行为。它可能是高血压性巩膜重塑的潜在治疗靶点。
