ZBTB38, a novel regulator of autophagy initiation targeted by RB1CC1/FIP200 in spinal cord injury

Chen, Jie; Li, Yan; Wang, Haosen; Zhang, Zengmeng; Yu, Daolun; Cheng, Xing; Li, Jie; Li, Honglin; Li, Jun; Cai, Yafei

doi:10.1016/j.gene.2018.07.073

Cited by 7 publications

(4 citation statements)

References 42 publications

(56 reference statements)

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“…Autophagy helps regulate cellular stress, and factors that inhibit autophagic activities may lead to cellular damages (36). To further investigate whether TGF-β1 regulates cell viability through PI3KC3-mediated autophagy regulation, the cellular autophagic activities were detected.…”

Section: Resultsmentioning

confidence: 99%

Regulation of TGF‑β1 on PI3KC3 and its role in hypertension‑induced vascular injuries

2018

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The aim of the present study was to investigate the expression and role of transforming growth factor (TGF)-β1/phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3) in the peripheral blood in patients with hypertension. A total of 28 patients with primary hypertension and 20 healthy control subjects were included. Peripheral blood samples were collected. The mRNA and protein expression levels were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell counting kit-8 assay, Transwell chamber assay and flow cytometry were performed to detect the cell proliferation, migration ability and cellular apoptosis, respectively. Laser scanning confocal microscopy was used to detect the intracellular autophagosomes. The expression of TGF-β1 was significantly elevated, whereas the expression of PI3KC3 was significantly downregulated in the patients with hypertension compared with controls. There was negative correlation between the TGF-β1 and PI3KC3 expression. Following treatment with TGF-β1, the protein expression of PI3KC3 was significantly decreased in human umbilical vein endothelial cells (HUVECs), and the autophagic activity was significantly decreased. Furthermore, following the treatment of TGF-β1 the proliferation of HUVECs was significantly reduced in the HUVECs, the hypoxia-induced apoptosis rates were significantly elevated and the number of penetrating cells were significantly declined (indicating declined migration ability). However, the overexpression of PI3KC3 significantly ameliorated the proliferation, migration ability and hypoxia tolerance of TGF-β1-treated HUVECs. In conclusion, the present results indicated that TGF-β1 expression was elevated in the peripheral blood in hypertensive patients and negatively correlated with the PI3KC3 expression; and that TGF-β1 regulates the PI3KC3 signaling pathway to inhibit the autophagic activity of vascular endothelial cells, and regulate the cell proliferation, migration and anti-apoptosis ability, thus aggregating the endothelial cell injuries in hypertension. The results of the current study revealed a novel mechanism of TGF-β1 in the regulation of endothelial cell injury in hypertension, which may provide a potential target for disease therapy.

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Section: Resultsmentioning

confidence: 99%

Regulation of TGF‑β1 on PI3KC3 and its role in hypertension‑induced vascular injuries

2018

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“…hUNG is highly effective at removing deaminated cytosine and mis-incorporated uracil from single-stranded DNA, which is abundant in replicating cells [ 36 ]. High expression of Zbtb38 can promote autophagy and partly rescue the secondary damage caused by SCI [ 37 ]. Zbtb4 is a mammalian DNA-binding protein, contains C 2 H 2 zinc fingers and a BTB/POZ domain, and functions as a transcriptional repressor [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization and Clinical Characteristics of m5C-Based RNA Methylation in Spinal Cord Injury: Validated by qPCR

Cao

Zhang

et al. 2022

International Journal of Genomics

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Aberrant patterns of 5-methylcytosine (m5C)-based ribonucleic acid (RNA) methylation have critical roles in various human diseases, but their importance in spinal cord injury (SCI) is largely unknown. We explore the expression patterns and potential roles of m5C-based regulators of RNA modification after SCI. We analyzed 16 m5C-based regulators of RNA modification in tissues with SCI and normal rats from the Gene Expression Omnibus database. We constructed a “gene signature” of m5C-based regulators of RNA modification to predict the prognosis of SCI using least absolute shrinkage and selection operator regression and random-forest strategy. We found that the m5C-related genes, deoxyribonucleic acid (DNA) methyltransferase1 (Dnmt1), methyl-CpG binding domain protein 2 (Mbd2), ubiquitin-like with PHD and ring finger domains 1 (Uhrf1), uracil-N-glycosylase (Ung), and zinc finger and BTB(brica-brac, tramtrack, and broad) domain containing 38 (Zbtb38) had high expression, and zinc finger and BTB domain containing 4 (Zbtb4) had low expression in SCI. Analysis of the correlation between the gene sets of m5C-based regulators of RNA modification and immune-cell infiltration and immune response revealed Dnmt1, DNA methyltransferases 3A (Dnmt3a), Mbd2, and Ung to be positive regulators of the immune microenvironment, and Zbtb4 may negatively regulate the immune environment. Then, two molecular subtypes were identified based on 16 m5C-regulated genes. Functional-enrichment analysis of differentially expressed genes between different patterns of m5C-based modification was undertaken. Through the creation of a protein–protein interaction network, we screened 11 hub genes. We demonstrated their importance between SCI group and sham group using real-time reverse transcription-quantitative polymerase chain reaction in rat model. Expression of hub genes did not correlate with mitophagy but was positively correlated with endoplasmic reticulum stress (ERS), which suggested that there may be differences in ERS between different patterns of m5C-based modification. This present study explored and discovered the close link between m5C regulators-related genes and SCI. We also hope our findings may contribute to further mechanistic and therapeutic research on the role of key m5C regulators after SCI.

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“…A favorable microenvironment for neurogenesis and the restoration of fully transected spinal cord function is provided by the neurotrophin-3 (NT3)-loaded chitosan, which has been shown through transcriptome analysis to be essential for the spinal cord's regenerative effects (34). After SCI, apoptosis is also unavoidable, and ZBTB38 overexpression significantly increases RB1CC1, a crucial element of the spinal cord's autophagy initiation mechanism, promoting autophagy and partially reversing secondary damage (35). Similar to this, increased miRNA-21 expression levels following SCI may aid in spinal cord repair by inhibiting the expression of its target gene, PDCD4 (36).…”

Section: Transcriptomicsmentioning

confidence: 99%

Multi-omics in Spinal Cord Injury: Diagnosis, Prognosis, and Treatment

Xu¹,

Zhao²,

Zhou³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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ZBTB38, a novel regulator of autophagy initiation targeted by RB1CC1/FIP200 in spinal cord injury

Cited by 7 publications

References 42 publications

Regulation of TGF‑β1 on PI3KC3 and its role in hypertension‑induced vascular injuries

Regulation of TGF‑β1 on PI3KC3 and its role in hypertension‑induced vascular injuries

Molecular Characterization and Clinical Characteristics of m5C-Based RNA Methylation in Spinal Cord Injury: Validated by qPCR

Multi-omics in Spinal Cord Injury: Diagnosis, Prognosis, and Treatment

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