Effect of zymosan on the expression and function of the gap-junction protein connexin 43 in human corneal fibroblasts  

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作  者:Xiao-Shuo Zheng Hui Zheng Dan Xu Ping-Ping Liu Bing Li Zi-Mu Cao Yang Liu Ye Liu 

机构地区:[1]Department of Ophthalmology,the Fith Affiliated Hospital,Sun Yat-sen University,Zhuhai 5190001 Guangzhou Province,China [2]Institute of Enironmental Systems Biology,Environmental Science and Enginecring College,Dalian Maritime University,Dalian 116027,Liaoning Province,China [3]Department of Pathology,the Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai 519000,Guangzhou Province,China

出  处:《International Journal of Ophthalmology(English edition)》2021年第3期341-348,共8页国际眼科杂志(英文版)

基  金:Supported by the National Natural Science Foundation of China(No.81770889);the Natural Science Foundation of Guangdong Province(No.2018A030313428);the Zhuhai Science and Technology Program(No.20191210E030077)。

摘  要:AIM:To study the effect of zymosan,a ligand found on the surface of fungi,on gap junctional intercellular communication(GJIC)in cultured human corneal fibroblasts(HCFs).METHODS:Zymosan was added to the medium of cultured HCFs with or without the administration of mitogenactivated protein kinase(MAPK)inhibitors or the inhibitor kappa B kinase 2(IKK2)inhibitor IV.The protein and m RNA levels of connexin 43(Cx43)in HCFs were measured by Western blot,immunofluorescence,and quantitative reverse transcription-polymerase chain reaction(q RT-PCR)analyses.The GJIC activity was tested using a dye-coupling assay.RESULTS:The reduction of Cx43 protein and m RNA levels as well as a significant decrease in GJIC activity were observed in cultured HCFs when zymosan was added into the culture medium.Compared with controls(no zymosan),the protein level of Cx43 was reduced by 45%and 54%in the presence of zymosan at 200 and 600μg/m L,respectively(P<0.05);and it was reduced by 45%,48%,and 75%in the presence of zymosan(600μg/m L)for 24,36,and 48 h,respectively(P<0.05).The m RNA expression of Cx43 was reduced by 98%in the presence of zymosan(P<0.05).The effects of zymosan on Cx43 expression and GJIC activity were attenuated by the administration of PD98059[an extracellular signal-regulated kinase(ERK)signaling inhibitor](P<0.05),c-Jun NH2-terminal kinase(JNK)inhibitor II(P<0.05),and IKK2 inhibitor IV(P<0.05).CONCLUSION:Zymosan inhibits the activity of GJIC in cultured HCFs.This effect is likely regulated via the nuclear factor-κB(NF-κB),MAPK/ERK,and JNK signaling pathways.The inhibitory effects of zymosan on Cx43 expression and GJIC activity in HCFs may induce damage of corneal stroma during corneal fungal infection.

关 键 词:corneal fibroblast ZYMOSAN gap junction connexin 43 MAPKS 

分 类 号:R772.21[医药卫生—眼科]

 

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