M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression

Liang, En; Xiao, Shaorong; Zhao, Changtong; Zhang, Yu; Fu, Guanglei

doi:10.1016/j.heliyon.2023.e16905

Cited by 6 publications

(2 citation statements)

References 42 publications

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“…In addition, many studies have reported the role of m6A methylation in programmed cell death including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis 13 . An increasing understanding of the regulatory mechanisms associated with m6A has led to numerous investigations into the role of m6A-related molecules in I/R injury in organs such as the heart 14,15 , brain 16,17 , and kidney 18,19 . For instance, m6A peaks and genes in the liver were higher in the I/R group than in the sham group using methylated RNA immunoprecipitation and high-throughput sequencing (MeRIP-seq) 20 .…”

Section: Introductionmentioning

confidence: 99%

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway

Gao,

Wang,

Qin

et al. 2024

Preprint

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Inflammatory responses, apoptosis, and oxidative stress, are key factors that contribute to hepatic ischemia/reperfusion (I/R) injury, which may lead to the failure of liver surgeries, such as hepatectomy and liver transplantation. The N6-methyladenosine (m6A) modification has been implicated in multiple biological processes, and its specific role and mechanism in hepatic I/R injury require further investigation. This study focused on the role of RNA methylase METTL3 in hepatic ischemia-reperfusion injury. Dot blotting analysis was used to profile m6A levels in liver tissues at different reperfusion time points in hepatic I/R mouse models. Hepatocyte-specific METTL3 knockdown (HKD) mice were used to determine the function of METTL3 during hepatic I/R. RNA sequencing and western blotting were performed to assess the potential signaling pathways involved with the deficiency of METTL3. Finally, AAV8-TBG-METTL3 was injected through the tail vein to further elucidate the role of METTL3 in hepatic I/R injury. We found that the m6A modification levels and the expression of METTL3 were upregulated in mouse livers during hepatic I/R injury. METTL3 deficiency led to an exacerbated inflammatory response and increased cell death during hepatic I/R, whereas overexpression of METTL3 reduced the extent of liver injury. Bioinformatic analysis revealed that the MAPK pathway was significantly enriched in the livers of METTL3-deficient mice. METTL3 protected the liver from I/R injury, possibly by inhibiting the phosphorylation of JNK and ERK, but not P38.

show abstract

Section: Introductionmentioning

confidence: 99%

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway

Gao,

Wang,

Qin

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, many studies have reported the role of m 6 A methylation in programmed cell death including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis 13 . An increasing understanding of the regulatory mechanisms associated with m 6 A has led to numerous investigations into the role of m 6 A-related molecules in I/R injury in organs such as the heart 14 , 15 , brain 16 , 17 , and kidney 18 , 19 . For instance, m 6 A peaks and genes in the liver were higher in the I/R group than in the sham group using methylated RNA immunoprecipitation and high-throughput sequencing (MeRIP-seq) 20 .…”

Section: Introductionmentioning

confidence: 99%

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway

Gao,

Wang,

Qin

et al. 2024

Int. J. Med. Sci.

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Background: Inflammatory responses, apoptosis, and oxidative stress, are key factors that contribute to hepatic ischemia/reperfusion (I/R) injury, which may lead to the failure of liver surgeries, such as hepatectomy and liver transplantation. The N6-methyladenosine (m 6 A) modification has been implicated in multiple biological processes, and its specific role and mechanism in hepatic I/R injury require further investigation. Methods: Dot blotting analysis was used to profile m 6 A levels in liver tissues at different reperfusion time points in hepatic I/R mouse models. Hepatocyte-specific METTL3 knockdown (HKD) mice were used to determine the function of METTL3 during hepatic I/R. RNA sequencing and western blotting were performed to assess the potential signaling pathways involved with the deficiency of METTL3. Finally, AAV8-TBG-METTL3 was injected through the tail vein to further elucidate the role of METTL3 in hepatic I/R injury. Results: The m 6 A modification levels and the expression of METTL3 were upregulated in mouse livers during hepatic I/R injury. METTL3 deficiency led to an exacerbated inflammatory response and increased cell death during hepatic I/R, whereas overexpression of METTL3 reduced the extent of liver injury. Bioinformatic analysis revealed that the MAPK pathway was significantly enriched in the livers of METTL3-deficient mice. METTL3 protected the liver from I/R injury, possibly by inhibiting the phosphorylation of JNK and ERK, but not P38. Conclusions: METTL3 deficiency aggravates hepatic I/R injury in mice by activating the MAPK signaling pathway. METTL3 may be a potential therapeutic target in hepatic I/R injury.

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Usf2 Deficiency Promotes Autophagy to Alleviate Cerebral Ischemia-Reperfusion Injury Through Suppressing YTHDF1-m6A-Mediated Cdc25A Translation

Liu,

Gao,

Dong

et al. 2023

Mol Neurobiol

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M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression

Cited by 6 publications

References 42 publications

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway

Usf2 Deficiency Promotes Autophagy to Alleviate Cerebral Ischemia-Reperfusion Injury Through Suppressing YTHDF1-m6A-Mediated Cdc25A Translation

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