Perfluorooctane sulfonate (PFOS) disrupts blood-testis barrier by down-regulating junction proteins via p38 MAPK/ATF2/MMP9 signaling pathway

Qiu, Lianglin; Qian, Yue; Liu, Zhenzhen; Wang, Chao; Qu, Junle; Wang, Xiaoke; Wang, Shoulin

doi:10.1016/j.tox.2016.11.003

Cited by 83 publications

(43 citation statements)

References 43 publications

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“…MMP9 can perturb various blood-tissue barriers [34,38]. Therefore, we further investigated the effects of ZIKV on the permeability of the SCB in vitro.…”

Section: Zikv Infection Increased the Permeability Of An In Vitro Scbmentioning

confidence: 99%

“…MMP9 facilitates Zika virus entry into the testis According to previous studies, transepithelial electrical resistance (TEER) is widely implicated as a marker for the integrity of the BTB [38], and decreased TEER in cells indicates the hyperpermeability of BTB. Thus, because SCs are central to the maintenance of BTB integrity, we next utilized primary mSCs as an in vitro SCB model to evaluate TEER.…”

Section: Plos Pathogensmentioning

confidence: 99%

“…As described previously [38], SCs were isolated from the testes of 6-10-day-old male WT C57BL/6 mice. Briefly, freshly isolated testes were washed with precooled PBS, the white membrane outside the testes was gently removed, and the testes were then into small pieces.…”

Section: Isolation Of Scsmentioning

confidence: 99%

“…As described previously [25,38], to evaluate the effects of MMP9 on the integrity of the SCB, 2.5 × 10 5 primary mSCs were plated on a 12-well Transwell polycarbonate membrane system (Corning Life Sciences, Corning, NY, USA) with a 0.4-μm pore size and a 1.12-cm 2 membrane surface. The integrity of this in vitro SCB model was determined by measuring TEER using an epithelial volt/ohm meter (Evomx) with "chopstick" electrodes (World Precision Instrument) every day from day 2 after seeding.…”

Section: Teermentioning

confidence: 99%

“…The integrity of this in vitro SCB model was determined by measuring TEER using an epithelial volt/ohm meter (Evomx) with "chopstick" electrodes (World Precision Instrument) every day from day 2 after seeding. Experiments were performed with a high resistance until TEER values crossed 50 O • cm 2 , depending on the cell type, indicating 100% cell confluency [38]. Subsequently, cells were infected with ZIKV (MOI = 5) and then treated with or without the specific MMP9 inhibitor JNJ0966 for 1h.…”

Section: Teermentioning

confidence: 99%

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Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

Hui

Nie

et al. 2020

PLoS Pathog

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Zika virus (ZIKV) is a unique flavivirus with high tropism to the testes. ZIKV can persist in human semen for months and can cause testicular damage in male mice. However, the mechanisms through which ZIKV enters the testes remain unclear. In this study, we revealed that matrix metalloproteinase 9 (MMP9) was upregulated by ZIKV infection in cell culture and in A129 mice. Furthermore, using an in vitro Sertoli cell barrier model and MMP9-/mice, we found that ZIKV infection directly affected the permeability of the bloodtestis barrier (BTB), and knockout or inhibition of MMP9 reduced the effects of ZIKV on the Sertoli cell BTB, highlighting its role in ZIKV-induced disruption of the BTB. Interestingly, the protein levels of MMP9 were elevated by ZIKV nonstructural protein 1 (NS1) in primary mouse Sertoli cells (mSCs) and other cell lines. Moreover, the interaction between NS1 and MMP9 induced the K63-linked polyubiquitination of MMP9, which enhanced the stability of MMP9. The upregulated MMP9 level led to the degradation of essential proteins involved in the maintenance of the BTB, such as tight junction proteins (TJPs) and type IV collagens. Collectively, we concluded that ZIKV infection promoted the expression of MMP9 which was further stabilized by NS1 induced K63-linked polyubiquitination to affect the TJPs/ type IV collagen network, thereby disrupting the BTB and facilitating ZIKV entry into the testes.

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“…MMP9 can perturb various blood-tissue barriers [34,38]. Therefore, we further investigated the effects of ZIKV on the permeability of the SCB in vitro.…”

Section: Zikv Infection Increased the Permeability Of An In Vitro Scbmentioning

confidence: 99%

Section: Plos Pathogensmentioning

confidence: 99%

Section: Isolation Of Scsmentioning

confidence: 99%

Section: Teermentioning

confidence: 99%

Section: Teermentioning

confidence: 99%

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Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

Hui

Nie

et al. 2020

PLoS Pathog

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1α,25‐dihydroxyvitamin D₃ supplementation alleviates perfluorooctanesulfonate acid‐induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response

Liang

et al. 2022

Environmental Toxicology

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Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ).Our results showed that 1α,25(OH) 2 D 3 intervention significantly improved PFOSinduced sperm quality decline and testicular damage. Moreover, 1α,25(OH) 2 D 3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH) 2 D 3 ameliorated PFOS-induced augment of Nrf2 and target genes.These findings indicated that 1α,25(OH) 2 D 3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress. K E Y W O R D S 1α,25(OH) 2 D 3 , Nrf2, oxidative stress, perfluorooctanesulfonate acid, reproductive toxicity 1 | INTRODUCTION Perfluorooctanesulfonic acid (PFOS) is a representative synthetic organo-fluorine compound, which has been widely used as a stain repellent and anti-stick material due to its excellent hydrophobic and lipophobic properties. 1 However, PFOS is difficult to degrade and widely exists in water, dust, soil, and other environmental media. 2,3 Noteworthy, PFOS generates a bioaccumulation effect. Drinking water, contaminated food consumption, product usage, and occupational exposure are the main approaches to PFOS exposure. PFOS has been extensively detected in human blood, umbilical cord blood, breast milk, and other samples worldwide. 4 Therefore, PFOS exposure has become a global environmental problem, and it is of great importance to clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies.In human body, PFOS combines with proteins, such as liver fatty acid transporters in the liver and albumin in the plasma. Liver is the primary target of PFOS, which can cause typical hepatic toxicity by disrupting glucose and lipid metabolism. [5][6][7][8] Recent studies have discovered that PFOS can also induce immune toxicity, 9 cardiotoxicity, 10 and neurotoxicity. 11 Furthermore, PFOS has significant reproductive

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A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS)

et al. 2023

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Perfluorooctane sulfonate (PFOS) disrupts blood-testis barrier by down-regulating junction proteins via p38 MAPK/ATF2/MMP9 signaling pathway

Cited by 83 publications

References 43 publications

Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

1α,25‐dihydroxyvitamin D₃ supplementation alleviates perfluorooctanesulfonate acid‐induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response

A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS)

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Perfluorooctane sulfonate (PFOS) disrupts blood-testis barrier by down-regulating junction proteins via p38 MAPK/ATF2/MMP9 signaling pathway

Cited by 83 publications

References 43 publications

Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

1α,25‐dihydroxyvitamin D3 supplementation alleviates perfluorooctanesulfonate acid‐induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response

A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS)

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Product

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1α,25‐dihydroxyvitamin D₃ supplementation alleviates perfluorooctanesulfonate acid‐induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response