Microcystin-leucine-arginine causes blood-testis barrier disruption and degradation of occludin mediated by matrix metalloproteinase-8

Cellular and Molecular Life Sciences : CMLS
Yabing ChenXiaodong Han

Abstract

Microcystin-leucine-arginine (MC-LR) can cause male reproductive disorders. However, the underlying mechanisms are not yet fully understood. In this study, we aimed to investigate the effects of MC-LR on the integrity of blood-testis barrier (BTB) and the related molecular mechanisms. Both transepithelial electrical resistance measurement in vitro and electron microscope observation ex vivo revealed that MC-LR caused disruption of the tight junction between Sertoli cells, which was paralleled by the degradation of occludin. We observed increased expression of matrix metalloproteinase-8 (MMP-8) upon exposure to MC-LR, and confirmed that abrogation of MMP-8 activity by specific inhibitors as well as transfection with MMP-8 shRNA could abolish the degradation of occludin. Our data demonstrated that MC-LR up-regulated nuclear levels of c-Fos and c-Jun through activating ERK and JNK, and increased NF-κB levels by activating the phosphatidylinositol 3-kinase (PI3K)/AKT cascades. Enhanced binding of c-Fos and NF-κB to the promoter of MMP-8 promoted the transcription of MMP-8 gene. Furthermore, miR-184-3p was significantly downregulated in SC following exposure to MC-LR through targeting MMP-8 expression. Together, these results confir...Continue Reading

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Citations

Nov 16, 2018·Journal of Toxicology and Environmental Health. Part a·Cong WenFei Yang
May 16, 2020·Climacteric : the Journal of the International Menopause Society·H-L ZuoH Du
Sep 30, 2020·Biological Trace Element Research·Tianjiao LuShuxia Guo
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Jun 3, 2021·Environment International·Ya MaHuizhen Zhang
Feb 2, 2022·Cellular and Molecular Life Sciences : CMLS·Shuxian WangBing Yao

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
transfection
immunoprecipitation
PCR
electron microscopy
electrophoresis
ChIP

Software Mentioned

SPSS

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