General Information of the Disease (ID: M6ADIS0120)
Name
Congenital pneumonia
ICD
ICD-11: KB24
Full List of Target Gene(s) of This m6A-centered Disease Response
Histone-lysine N-methyltransferase EZH2 (EZH2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary METTL3 promotes inflammation and cell apoptosis in a pediatric pneumonia model by regulating Histone-lysine N-methyltransferase EZH2 (EZH2).
Responsed Disease Congenital pneumonia [ICD-11: KB24]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Inflammation
In-vitro Model HPBM (Human Peripheral Blood Monocytes)
Signal transducer and activator of transcription 2 (STAT2)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary SNHG4 was downregulated in the neonatal pneumonia patient serum and its overexpression could inhibit LPS induced inflammatory injury in human lung fibroblasts and mouse lung tissue. The molecular mechanism underlying this protective effect was achieved by suppression of METTL3-mediated m6A modification levels of YTHDF1-dependent Signal transducer and activator of transcription 2 (STAT2) mRNA.
Responsed Disease Congenital pneumonia [ICD-11: KB24]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Cell Process Cell apoptosis
In-vitro Model WI-38 Normal Homo sapiens CVCL_0579
In-vivo Model All mice were housed under a 12 h light/dark cycle with constant temperature about 25 ℃ and relative humidity approximating 55 %. The mice had free access to food and water for 10 days prior to the experiment. Forty mice were randomly selected and divided into four groups of 10 mice each. After 10 days, mice received an intraperitoneal injection of 22 mg / mL sodium pentobarbital (diluted in saline) followed by 167 uM LPS (60 uL) Saline solution was instilled into the oral cavity through the posterior pharyngeal wall. Pinch the nares quickly and hold for 30 s, model is successful when all fluid is absorbed into the nasal cavity, and slight tracheal rales appear. Lentiviral vectors containing pcDNA-SNHG4 (150 uM) or pcDNA-3.1 were intratracheally injected into mice. Twenty-one days after establishing the model, mice were intraperitoneally injected with 3% sodium pentobarbital and euthanized by overdose anesthesia at a dose of 90 mL/Kg, and organs and tissues were removed for follow-up studies.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary SNHG4 was downregulated in the neonatal pneumonia patient serum and its overexpression could inhibit LPS induced inflammatory injury in human lung fibroblasts and mouse lung tissue. The molecular mechanism underlying this protective effect was achieved by suppression of METTL3-mediated m6A modification levels of YTHDF1-dependent Signal transducer and activator of transcription 2 (STAT2) mRNA.
Responsed Disease Congenital pneumonia [ICD-11: KB24]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Down regulation
Cell Process Cell apoptosis
In-vitro Model WI-38 Normal Homo sapiens CVCL_0579
In-vivo Model All mice were housed under a 12 h light/dark cycle with constant temperature about 25 ℃ and relative humidity approximating 55 %. The mice had free access to food and water for 10 days prior to the experiment. Forty mice were randomly selected and divided into four groups of 10 mice each. After 10 days, mice received an intraperitoneal injection of 22 mg / mL sodium pentobarbital (diluted in saline) followed by 167 uM LPS (60 uL) Saline solution was instilled into the oral cavity through the posterior pharyngeal wall. Pinch the nares quickly and hold for 30 s, model is successful when all fluid is absorbed into the nasal cavity, and slight tracheal rales appear. Lentiviral vectors containing pcDNA-SNHG4 (150 uM) or pcDNA-3.1 were intratracheally injected into mice. Twenty-one days after establishing the model, mice were intraperitoneally injected with 3% sodium pentobarbital and euthanized by overdose anesthesia at a dose of 90 mL/Kg, and organs and tissues were removed for follow-up studies.
References
Ref 1 METTL3 promotes inflammation and cell apoptosis in a pediatric pneumonia model by regulating EZH2. Allergol Immunopathol (Madr). 2021 Sep 1;49(5):49-56. doi: 10.15586/aei.v49i5.445. eCollection 2021.
Ref 2 Long noncoding RNA SNHG4 remits lipopolysaccharide-engendered inflammatory lung damage by inhibiting METTL3 - Mediated m(6)A level of STAT2 mRNA. Mol Immunol. 2021 Nov;139:10-22. doi: 10.1016/j.molimm.2021.08.008. Epub 2021 Aug 25.