Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK/NF‐κB signaling

Zhao, Yulin; Zong, Fang

doi:10.1002/iid3.465

Cited by 14 publications

(6 citation statements)

References 32 publications

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“…5A-B). According to the literature, Adrenomedullin2 (ADM2), activating transcription factor 6 (ATF6), CANX, Endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 1 (EDEM1), Mesencephalic astrocyte-derived neurotrophic factor (MANF), and Ubiquitin-speci c protease 14 (USP14) are closely linked with PE or Aβ [15][16][17][18][19][20], which further validated their expression levels in our study. Consistently, they were signi cantly differentially expressed in placental tissues of NP and PE, as well as in HTR-8/SVneo cells induced with or without TM (Fig.…”

Section: Identi Cation Of Degs Associated With the Upr In Pe And Thei...supporting

confidence: 79%

Aβ1-42 stimulates an increase in autophagic activity through tunicamycin-induced endoplasmic reticulum stress in HTR-8/SVneo cells and pre-eclampsia

Gao,

Cheng,

Cai

et al. 2024

Preprint

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Environmental changes can trigger endoplasmic reticulum (ER) stress and misfolded protein accumulation, potentially leading to Pre-eclampsia (PE). Amyloid-β (Aβ) is a crucial misfolded protein that can overactivate autophagy. Our study assessed the expression of Aβ1−42 and autophagic activity in PE placental tissues and trophoblasts under ER stress. Placental tissues were surgically collected from normal pregnant women (NP) and pregnant women with PE delivering through cesarean section. The expression levels of Aβ1−42 were detected in both PE and NP placental tissues, as well as in tunicamycin (TM)-induced HTR-8/SVneo cells. Autophagy-related proteins, such as Beclin-1, the ratio of LC3-II to LC3-I, ATG5, and SQSTM1/p62 in the placental tissues and HTR-8/SVneo cells were measured by Western blot. The number and morphology of autophagosomes were observed using transmission electron microscopy (TEM). Potential targets associated with the unfolded protein response (UPR) in the placental tissues of NP and PE cases were screened using PCR Arrays. The misfolded protein was significantly upregulated in the PE group. In both Pre-eclampsia (PE) placental tissues and TM-induced HTR-8/SVneo cells, not only was Aβ1–42 upregulated, but also Beclin-1, ATG5, and LC3BII/I were significantly increased, accompanied by an increase in autophagosome count, while SQSTM1/P62 was downregulated. A total of 17 differentially expressed genes (DEGs) associated with the UPR were identified, among which elevated calnexin (CANX) was validated in the placenta from both PE and TM-induced HTR-8/SVneo cells. Autophagy is significantly upregulated in PE cases due to ER stress-induced Aβ1−42 accumulation, likely mediated by autophagy-related proteins involved in the UPR.

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Section: Identi Cation Of Degs Associated With the Upr In Pe And Thei...supporting

confidence: 79%

Aβ1-42 stimulates an increase in autophagic activity through tunicamycin-induced endoplasmic reticulum stress in HTR-8/SVneo cells and pre-eclampsia

Gao,

Cheng,

Cai

et al. 2024

Preprint

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“…USP14, an important member of the USP protein family, participates in a variety of cellular signaling pathways, such as Wnt/β catenin and MAPK/NF-κB [ 34 , 35 ]. Previous studies have revealed that the biological functions of USP14 are regulated by its proteasome and post-modifications [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Ceramide Synthase 1 Inhibits Brain Metastasis of Non-Small Cell Lung Cancer by Interacting with USP14 and Downregulating the PI3K/AKT/mTOR Signaling Pathway

Pan

et al. 2023

Cancers

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Brain metastasis (BM) is common in patients with non-small cell lung cancer (NSCLC) and is associated with a poor prognosis. Ceramide synthase 1 (CERS1) participates in malignancy development, but its potential role in NSCLC BM remains unclear. This study aimed to explore the physiological effects and molecular mechanism of CERS1 in NSCLC BM. CERS1 expression was evaluated in NSCLC tissues and cell lines, and its physiological roles were subsequently explored in vivo and in vitro. Mass spectrometry and co-immunoprecipitation were performed to explore CERS1-interacting proteins. The associated signaling pathways of CERS1 in NSCLC BM were further investigated using bioinformatics analysis and molecular biotechnology. We demonstrated that CERS1 was significantly downregulated in NSCLC cell lines and BM tissues, and its upregulation was associated with better prognoses. In vitro, CERS1 overexpression inhibited cell migration, invasion, and the ability to penetrate the blood-brain barrier. Moreover, CERS1 interacted with ubiquitin-specific protease 14 (USP14) and inhibited BM progression by downregulating the PI3K/AKT/mTOR signaling pathway. Further, CERS1 expression substantially suppressed BM tumor formation in vivo. This study demonstrated that CERS1 plays a suppressor role in NSCLC BM by interacting with USP14 and downregulating the PI3K/AKT/mTOR signaling pathway, thereby serving as a novel therapeutic target for NSCLC BM.

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“…However, b-AP15 not only regulates UCHL5, but also acts on USP14. It has been reported that USP14 may up-regulate the production of pro-inflammatory cytokines through the NF-κB pathway 51 , and USP14 may enhance the dedifferentiation effect of IL-1β on chondrocytes 52 . Recently, an inhibitor of UCHL5 was designed by possibly blocking its deubiquitinating function, and contributed to the accumulation of polyubiquitinated substrates 53 .…”

Section: Discussionmentioning

confidence: 99%

NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs

Zhao¹,

Cao²,

Chen³

et al. 2023

Int. J. Biol. Sci.

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NLRP3 has been involved in several physiological and pathological processes. However, the role and mechanism of NLRP3 activation in mandibular healing remain unclear. Here, a full-thickness mandibular defect model by osteotomy was established in wild-type (WT) and Prx1-Cre/ROSA nTnG mice to demonstrate the NLRP3 inflammasome activation in mandibular healing. We found that NLRP3 was activated in mesenchymal stem cells (MSCs)-mediated mandibular healing and was prominent in Prx1 + cells. Inhibition of NLRP3 exerted a positive effect on bone formation without changing the number of Prx1-cre + cells in the defect areas. In addition, NLRP3 deficiency promoted osteoblast differentiation. We next screened for the deubiquitinating enzymes that were previously reported to be associated with NLRP3, and identified UCHL5 as a regulator of NLRP3 activation in mandibular healing. Mechanistically, NLRP3 directly bound to UCHL5 and maintained its stability through reducing ubiquitin-proteasome pathway degradation in mandibular MSCs. At last, UCHL5 inhibition enhanced osteoblast differentiation by promoting NLRP3 ubiquitination and degradation. Thus, our results provided the proof that NLRP3 acted as a negative modulator in mandibular healing and extended the current knowledge regarding posttranslational modification of NLRP3 by UCHL5.

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Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK/NF‐κB signaling

Cited by 14 publications

References 32 publications

Aβ1-42 stimulates an increase in autophagic activity through tunicamycin-induced endoplasmic reticulum stress in HTR-8/SVneo cells and pre-eclampsia

Aβ1-42 stimulates an increase in autophagic activity through tunicamycin-induced endoplasmic reticulum stress in HTR-8/SVneo cells and pre-eclampsia

Ceramide Synthase 1 Inhibits Brain Metastasis of Non-Small Cell Lung Cancer by Interacting with USP14 and Downregulating the PI3K/AKT/mTOR Signaling Pathway

NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs

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