标题：CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13
作者：Gao, Nan; Liu, Xiaowei; Wu, Jiayin; Li, Juan; Dong, Chen; Wu, Xinyi; Xiao, Xiao; Yu, Fu-Shin X.
作者机构：[Gao, Nan; Yu, Fu-Shin X.] Wayne State Univ, Sch Med, Dept Ophthalmol, Kresge Eye Inst, 4717 St Antoine Blvd, Detroit, MI 48201 USA.; [Gao, Nan; Yu, 更多
通讯作者：Yu, FSX;Yu, FSX
通讯作者地址：[Yu, FSX]Wayne State Univ, Sch Med, Dept Ophthalmol, Kresge Eye Inst, 4717 St Antoine Blvd, Detroit, MI 48201 USA;[Yu, FSX]Wayne State Univ, Dept Anat 更多
关键词：Angiogenesis; Candida albicans keratitis; CXCL10; Cornea
摘要：Though not present in the normal adult cornea, both hem- and lymph-angiogenesis can be induced in this tissue after an inflammatory, infectious, or traumatic insult. We previously showed that the chemokine CXCL10 plays a key role in eradicating invading Candida (C.) albicans in C57BL6 mouse corneas. However, even after the clearance of pathogens, infection-induced inflammation and angiogenesis continue to progress in the cornea. The aim of this study is define the role of CXCL10 as a major angiostatic factor in modulating cornea angiogenesis in B6 mouse corneas under pathogenic conditions. We showed that epithelial expression of CXCL10, driven by AAV9 vector, suppressed both infection- and inflammation-induced hem and lymph angiogenesis, whereas the neutralization of CXCL10 as well as its receptor CXCR3 greatly promoted these processes. The inhibitory effect of CXCL10 was unrelated to its antimicrobial activity, but through the suppression of the expression of many angiogenic factors, including VEGFa and c, and MMP-13 in vivo. Inhibition of MMP13 but not TIMPs, attenuated suture-induced neovascularization but had no effects on CXCL10 expression. Strikingly, topical application of CXCL10 post-C. albicans infection effectively blocked both hem- and lymph-angiogenesis and preserved the integrity of sensory nerves in the cornea. Taken together, CXCL10 has strong inhibitory effects on neovascularization, whereas MMP13 is required for neovascularization in C. albicans-infected corneas and the local application of CXCL10 or MMP13 inhibitors, alone or as adjuvant therapy, may target hem- and lymph-angiogenesis in the inflamed corneas.