m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0017)
Name
Hepatic fibrosis/cirrhosis
ICD
ICD-11: DB93
Full List of Target Gene(s) of This m6A-centered Disease Response
Protein patched homolog 1 (PTCH1)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary AcSDKP in liver fibrosis via m6A modification and Hedgehog pathway, which helps us to shed light on the molecular mechanism in liver fibrosis progression. WTAP targeted the 3'-UTR of Protein patched homolog 1 (PTCH1) mRNA, and administration of AcSDKP reduced the stability of Ptch1 mRNA.
Responsed Disease Hepatic fibrosis [ICD-11: DB93.0]
Responsed Drug AcSDKP Phase 2
 Drug Info 
Target Regulator Wilms tumor 1-associating protein (WTAP) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Hedgehog signaling pathway hsa04340
Cell Process Cell apoptosis
In-vitro Model HSC (Hematopoietic stem cell)
In-vivo Model Male Sprague-Dawley rats (375-400 g) liver fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) and olive oil (a ratio of 2:3) twice per week.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary ALKBH5 mediated Protein patched homolog 1 (PTCH1) activation via a m6A-dependent manner,ALKBH5 ameliorated liver fibrosis and suppressed HSCs activation via triggering PTCH1 activation in a m6A dependent manner.
Responsed Disease Hepatic fibrosis [ICD-11: DB93.0]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Hedgehog signaling pathway hsa04340
In-vitro Model HSCs (Hepatic stellate cells(HSCs) were purchased from American Type Culture Collections (Manassas, VA))
In-vivo Model Liver fibrosis mice model was induced by intraperitoneal CCl4 injection for 12 weeks. The dose regimen for CCl4 in mice is 1 ml kg-1, diluted to 50% with olive oil twice per week for 12 weeks. Until 11 weeks, mice with liver-specific disruption of ALKBH5 were given hydrodynamic tail-vein injections of LV5-ALKBH5.
References
Ref 1 N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) mitigates the liver fibrosis via WTAP/m(6)A/Ptch1 axis through Hedgehog pathway. Gene. 2022 Mar 1;813:146125. doi: 10.1016/j.gene.2021.146125. Epub 2021 Dec 16.
Ref 2 ALKBH5 ameliorated liver fibrosis and suppressed HSCs activation via triggering PTCH1 activation in an m(6)A dependent manner. Eur J Pharmacol. 2022 May 5;922:174900. doi: 10.1016/j.ejphar.2022.174900. Epub 2022 Mar 19.