Name	Idiopathic interstitial pneumonitis
ICD	ICD-11: CB03

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	PM2.5 exposure increased the levels of METTL3-mediated m6A modification of Cadherin-1 (CDH1) mRNA. PM2.5 exposure triggered EMT progression to promote the pulmonary fibrosis via miR-494-3p/YTHDF2 recognized and METTL3 mediated m6A modification.
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	ALKBH5 promotes silica-induced lung fibrosis via the miR-320a-3p/FOXM1 axis or targeting Forkhead box protein M1 (FOXM1) directly.
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	NIH 3T3	Normal	Mus musculus	CVCL_0594
	MRC-5	Normal	Homo sapiens	CVCL_0440
In-vivo Model	For the mouse model of miR-320a-3p overexpression, a total of 24 male C57BL/6 mice were divided randomly into four groups (n = 6 in each group): saline, silica, silica plus AAV9-miR-NC, and silica plus AAV9-miR-320a-3p. The mice in the silica plus AAV9-miR-NC/AAV9-miR-320a-3p groups were anesthetized using the same method, then administered intratracheally 50 uL AAV9-miR-NC/AAV9-miR-320a-3p per mouse at a titer of 8 × 1012 v. g./ml. Three weeks later, these mice were treated in the same way using anesthesia, saline, and silica as mentioned above. Subsequently, after 4 weeks, the mice were sacrificed, and the lungs were isolated and frozen at -80 ℃ for further study.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Lowering m6A levels through silencing METTL3 suppresses the FMT process in vitro and in vivo. m6A modification regulates EMT by modulating the translation of Potassium voltage-gated channel subfamily H member 6 (KCNH6) mRNA in a YTHDF1-dependent manner. Manipulation of m6A modification through targeting METTL3 becomes a promising strategy for the treatment of idiopathic pulmonary fibrosis.
Responsed Disease	Idiopathic pulmonary fibrosis [ICD-11: CB03.4]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	WI-38	Normal	Homo sapiens	CVCL_0579
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Animals were bred and housed in the pathogen-free facility of the Laboratory Animal Center of Shanghai General Hospital (Shanghai, China). All lungs were collected 4 weeks after BLM treatment for histology and further study. Lung microsections (5 uM) were applied to Masson's trichrome and Sirius red staining to visualize fibrotic lesions.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Lowering m6A levels through silencing METTL3 suppresses the FMT process in vitro and in vivo. m6A modification regulates EMT by modulating the translation of Potassium voltage-gated channel subfamily H member 6 (KCNH6) mRNA in a YTHDF1-dependent manner. Manipulation of m6A modification through targeting METTL3 becomes a promising strategy for the treatment of idiopathic pulmonary fibrosis.
Responsed Disease	Idiopathic pulmonary fibrosis [ICD-11: CB03.4]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	WI-38	Normal	Homo sapiens	CVCL_0579
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Animals were bred and housed in the pathogen-free facility of the Laboratory Animal Center of Shanghai General Hospital (Shanghai, China). All lungs were collected 4 weeks after BLM treatment for histology and further study. Lung microsections (5 uM) were applied to Masson's trichrome and Sirius red staining to visualize fibrotic lesions.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	m6A modification of pri-miRNA-126 and its binding with DGCR8 decreases blocked microRNA 126 (MIR126) maturation, and then activated the PI3K/AKT/mTOR pathway, which drove the fibro genesis in the lung after CB exposure.
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Pathway Response	MAPK signaling pathway			hsa04010
	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA maturation
In-vitro Model	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Rats inhaled CB at dose of 0, 5 or 30 mg/m3 for 28 days, 6 h/day, respectively. The rats inhaled CB at dose of 0 or 30 mg/m3 for 14 days, 28 days and 90 days, respectively. In vitro experiments, the normal human bronchial epithelial cell line (16HBE) was treated with CB (0, 50, 100 and 200 ug/mL) for 24 h.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	ALKBH5 promotes silica-induced lung fibrosis via the hsa-miR-320a-3p/FOXM1 axis or targeting FOXM1 directly.
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	NIH 3T3	Normal	Mus musculus	CVCL_0594
	MRC-5	Normal	Homo sapiens	CVCL_0440
In-vivo Model	For the mouse model of miR-320a-3p overexpression, a total of 24 male C57BL/6 mice were divided randomly into four groups (n = 6 in each group): saline, silica, silica plus AAV9-miR-NC, and silica plus AAV9-miR-320a-3p. The mice in the silica plus AAV9-miR-NC/AAV9-miR-320a-3p groups were anesthetized using the same method, then administered intratracheally 50 uL AAV9-miR-NC/AAV9-miR-320a-3p per mouse at a titer of 8 × 1012 v. g./ml. Three weeks later, these mice were treated in the same way using anesthesia, saline, and silica as mentioned above. Subsequently, after 4 weeks, the mice were sacrificed, and the lungs were isolated and frozen at -80 ℃ for further study.

Ref 1	N6-Methyladenosine Modification of CDH1 mRNA Promotes PM2.5-Induced Pulmonary Fibrosis via Mediating Epithelial Mesenchymal Transition. Toxicol Sci. 2022 Jan 24;185(2):143-157. doi: 10.1093/toxsci/kfab133.
Ref 2	ALKBH5 promotes lung fibroblast activation and silica-induced pulmonary fibrosis through miR-320a-3p and FOXM1. Cell Mol Biol Lett. 2022 Mar 12;27(1):26. doi: 10.1186/s11658-022-00329-5.
Ref 3	m(6)A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation. Mol Ther. 2021 Dec 1;29(12):3436-3448. doi: 10.1016/j.ymthe.2021.06.008. Epub 2021 Jun 8.
Ref 4	N(6)-methyladenosine-dependent primary microRNA-126 processing activated PI3K-AKT-mTOR pathway drove the development of pulmonary fibrosis induced by nanoscale carbon black particles in rats. Nanotoxicology. 2020 Feb;14(1):1-20. doi: 10.1080/17435390.2019.1661041. Epub 2019 Sep 10.