BaP/BPDE suppresses homologous recombination repair in human trophoblast cells to induce miscarriage: The roles of lnc-HZ08 DOI Creative Commons
Weina Chen, Chenglong Ma, Manli Wang

et al.

Environment International, Journal Year: 2024, Volume and Issue: 191, P. 108975 - 108975

Published: Aug. 24, 2024

Benzo(a)pyrene (BaP) or benzo (a) pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE) exposure causes trophoblast cell dysfunctions and induces miscarriage, which is generally epigenetically regulated. Homologous recombination (HR) repair of DNA double strand break (DSB) plays a crucial role in maintenance genetic stability normal functions. However, whether BaP/BPDE might suppress HR human cells to induce as well its epigenetic regulatory mechanism, largely unclear. In this study, we find that suppresses DSB eventually miscarriage by up-regulating lnc-HZ08. lnc-HZ08 (1) down-regulates the expression levels FOXA1 (forkhead box A1) thus FOXA1-mediated mRNA transcription BRCA1 (Breast cancer susceptibility gene 1) CtIP (CtBP-interacting protein), (2) impairs protein interactions competitive binding with through lnc-HZ08-1 fragment, also (3) BRCA1-mediated ubiquitination without affecting stability, three cells. Supplement murine Ctip could efficiently restore (i.e. increase) alleviate BaP-exposed mouse model. Collectively, study not only reveals association causality among exposure, defective repair, but discovers novel mechanism lnc-HZ08-regulated BRCA1/CtIP-mediated bridging regulation instability providing an efficient approach for treatment against BaP/BPDE-induced unexplained miscarriage.

Language: Английский

Disturbed shear stress promotes atherosclerosis through TRIM21‐regulated MAPK6 degradation and consequent endothelial inflammation DOI Creative Commons
Feng Wang, S Wang, Yue Gu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Rationale Coronary artery plaques often develop in regions subjected to disturbed shear stress (DSS), yet the mechanisms underlying this phenomenon remain poorly understood. Our study aimed elucidate unknown role of MAPK6 and plaque formation. Methods In vitro vivo experiments, RNA‐seq, CO‐IP proteomic analysis, combined with single‐cell RNA‐seq datasets were used reveal upstream downstream involved. AAV‐MAPK6, ApoE −/− flox/flox TEK Cre mice CXCL12 neutraligand confirm beneficial effects against atherosclerosis. Results revealed a substantial decrease protein levels endothelial cells response DSS, both vitro, which was contingent on binding ubiquitin ligase TRIM21 MAPK6. Endothelium‐specific overexpression exerts antiatherosclerotic mice, elucidating unexplored Comprehensive integrated mapping further experiments unveiled involvement inflammation through EGR1/CXCL12 axis. finally confirmed that conditional knockout resulted significant increases areas. Notably, these could be reversed neutralization CXCL12. Conclusions illuminates advantages decelerating progression, highlighting potential safeguarding as novel therapeutic strategy Key points Disturbed flow activates ubiquitin‒proteasome degradation pathway cells, is Endothelial has an advantageous impact progression. regulates via

Language: Английский

Citations

1
Organ-specific lithium accumulation and its toxic effects on female reproduction DOI

Qigang Fan,

Yi Sun, Qikun Shen

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138516 - 138516

Published: May 1, 2025

Language: Английский

Citations

0
Exposure to BaA Inhibits Trophoblast Cell Invasion and Induces Miscarriage by Regulating the DEC1/ARHGAP5 Axis and Promoting Ubiquitination-Mediated Degradation of MMP2 DOI
Lei Di, Tingting Chen, Cuifang Fan

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 479, P. 135594 - 135594

Published: Aug. 23, 2024

Language: Английский

Citations

2
BaP/BPDE suppresses homologous recombination repair in human trophoblast cells to induce miscarriage: The roles of lnc-HZ08 DOI Creative Commons
Weina Chen, Chenglong Ma, Manli Wang

et al.

Environment International, Journal Year: 2024, Volume and Issue: 191, P. 108975 - 108975

Published: Aug. 24, 2024

Benzo(a)pyrene (BaP) or benzo (a) pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE) exposure causes trophoblast cell dysfunctions and induces miscarriage, which is generally epigenetically regulated. Homologous recombination (HR) repair of DNA double strand break (DSB) plays a crucial role in maintenance genetic stability normal functions. However, whether BaP/BPDE might suppress HR human cells to induce as well its epigenetic regulatory mechanism, largely unclear. In this study, we find that suppresses DSB eventually miscarriage by up-regulating lnc-HZ08. lnc-HZ08 (1) down-regulates the expression levels FOXA1 (forkhead box A1) thus FOXA1-mediated mRNA transcription BRCA1 (Breast cancer susceptibility gene 1) CtIP (CtBP-interacting protein), (2) impairs protein interactions competitive binding with through lnc-HZ08-1 fragment, also (3) BRCA1-mediated ubiquitination without affecting stability, three cells. Supplement murine Ctip could efficiently restore (i.e. increase) alleviate BaP-exposed mouse model. Collectively, study not only reveals association causality among exposure, defective repair, but discovers novel mechanism lnc-HZ08-regulated BRCA1/CtIP-mediated bridging regulation instability providing an efficient approach for treatment against BaP/BPDE-induced unexplained miscarriage.

Language: Английский

Citations

1