Activation of Sonic Hedgehog Signaling Pathway Regulates Human Trabecular Meshwork Cell Function

作者全名："Wang, Xiaochen; Tan, Sisi; Yang, Shuang; Liu, Xianmao; Lei, Junqin; Li, Hong"

作者地址："[Wang, Xiaochen; Tan, Sisi; Yang, Shuang; Liu, Xianmao; Lei, Junqin; Li, Hong] Chongqing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Chongqing 400016, Peoples R China; [Wang, Xiaochen; Tan, Sisi; Yang, Shuang; Liu, Xianmao; Lei, Junqin; Li, Hong] Natl Clin Res Ctr Ocular Dis, Chongqing Eye Inst, Chongqing Branch, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China"

通信作者："Li, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Chongqing 400016, Peoples R China."

来源：JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001003000000001

JCR分区：Q2

影响因子：1.9

年份：2023

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期号：　

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结束页：　

文献类型：Article; Early Access

关键词：glaucoma; IOP; trabecular meshwork cells; Shh

摘要："Purpose: To investigate the effects of Sonic hedgehog (Shh) signaling on primary human trabecular meshwork (HTM) cells.Methods: Primary HTM cells were isolated from healthy donors and cultured. Recombinant Shh (rShh) protein and cyclopamine were used to activate and inhibit the Shh signaling pathway, respectively. A cell viability assay was performed to assess the effects of rShh on the activity of primary HTM cells. Functional assessment of cell adhesion and phagocytosis was also performed. The proportion of apoptotic cells was examined using flow cytometry. Fibronectin (FN) and transforming growth factor beta2 (TGF-beta 2) protein were detected to assess the influence of rShh on the metabolism of the extracellular matrix (ECM). Real-time polymerase chain reaction (RT-PCR) and western blot analyses were used to examine mRNA and protein expression of Shh signaling pathway-associated factors GLI Family Zinc Finger 1 (GLI1) and Suppressor of Fused (SUFU).Results: rShh significantly enhanced primary HTM cell viability at a concentration of 0.5 mu g/mL. rShh increased the adhesion and phagocytic abilities of primary HTM cells, and decreased cell apoptosis. FN and TGF-beta 2 protein expression increased in primary HTM cells treated with rShh. rShh upregulated the transcriptional activity and protein levels of GLI1, and downregulated those of SUFU. Correspondingly, the rShh-induced GLI1 upexpression was partially blocked by pretreatment with the Shh pathway inhibitor cyclopamine at a concentration of 10 mu M.Conclusions: Activation of Shh signaling can regulate the function of primary HTM cells through GLI1. Regulation of Shh signaling may be a potential target for attenuating cell damage in glaucoma."

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