A novel crosstalk between Nrf2 and Smad2/3 bridged by two nuanced Keap1 isoforms with their divergent effects on these distinct family transcription factors

Chen, Feilong; Wang, Qing; Xiao, Mei; Lou, Deshuai; Wufur, Reziyamu; Hu, Shaofan; Zhang, Zhengwen; Wang, Yeqi; Zhang, Yiguo

doi:10.1016/j.freeradbiomed.2024.01.025

Free Radical Biology and Medicine

2024

DOI: 10.1016/j.freeradbiomed.2024.01.025

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A novel crosstalk between Nrf2 and Smad2/3 bridged by two nuanced Keap1 isoforms with their divergent effects on these distinct family transcription factors

Feilong Chen,

Qing Wang,

Mei Xiao

et al.

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2024

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Cited by 2 publications

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Regulation of oxidative stress in the intestine of piglets after enterotoxigenic Escherichia coli (ETEC) infection

Jin,

Xu,

Yang

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Regulation of oxidative stress in the intestine of piglets after enterotoxigenic Escherichia coli (ETEC) infection

Jin,

Xu,

Yang

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Engineered Extracellular Vesicle-Based Nanoformulations That Coordinate Neuroinflammation and Immune Homeostasis, Enhancing Parkinson’s Disease Therapy

Zhang,

Shao,

Yuan

et al. 2024

ACS Nano

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Although conventional intervention to microglia can mitigate neuroinflammation in the short term, immune disorders by peripheral inflammatory cells can infiltrate continuously, resulting in an overactivated immune microenvironment of Parkinson’s disease (PD). Here, we design engineered extracellular vesicle-based nanoformulations (EVNs) to address multiple factors for the management of PD. Specifically, EVN is developed by coating CCR2-enriched mesenchymal stem cell-derived extracellular vesicles (MSCCCR2 EVs) onto a dihydrotanshinone I-loaded nanocarrier (MSeN-DT). The MSCCCR2 EVs (the shell of EVN) can actively show homing to specific chemokines CCL2 in the substantia nigra, which enables them to block the infiltration of peripheral inflammatory cells. Interestingly, MSeN-DT (the core of EVN) can promote the Nrf2–GPX4 pathway for the suppression of the source of inflammation by inhibiting ferroptosis in microglia. In the PD model mice, a satisfactory therapeutic effect is achieved, with inhibition of peripheral inflammatory cell infiltration, precise regulation of inflammatory microglia in the substantia nigra, as well as promotion of behavioral improvement and repairing damaged neurons. In this way, the combinatorial code of alleviation of inflammation and modulation of immune homeostasis can reshape the immune microenvironment in PD, which bridges internal anti-inflammatory and external immunity. This finding reveals a comprehensive therapeutic paradigm for PD that breaks the vicious cycle of immune overactivation.

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A novel crosstalk between Nrf2 and Smad2/3 bridged by two nuanced Keap1 isoforms with their divergent effects on these distinct family transcription factors

Cited by 2 publications

References 56 publications

Regulation of oxidative stress in the intestine of piglets after enterotoxigenic Escherichia coli (ETEC) infection

Regulation of oxidative stress in the intestine of piglets after enterotoxigenic Escherichia coli (ETEC) infection

Engineered Extracellular Vesicle-Based Nanoformulations That Coordinate Neuroinflammation and Immune Homeostasis, Enhancing Parkinson’s Disease Therapy

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