STM2457 is Therapeutic for Idiopathic Pulmonary Fibrosis by Inhibiting the METTL3-CTGF Signaling Axis

Moss B.J., Ryter S.W., Rosas I.O. 2022. Pathogenic mechanisms underlying idiopathic pulmonary fibrosis. Annu. Rev. Pathol. 17, 515–546.

CAS  PubMed  Google Scholar 

Shinde A.V., Humeres C., Frangogiannis N.G. 2017. The role of α-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. Biochim. Biophys. Acta, Mol. Basis Dis. 1863, 298–309.

CAS  Google Scholar 

Pardali E., Sanchez-Duffhues G., Gomez-Puerto M.C., Ten Dijke. P. 2017. TGF-β-induced endothelial-mesenchymal transition in fibrotic diseases. Int. J. Mol. Sci. 18, 2157.

PubMed  PubMed Central  Google Scholar 

Lu J., Shi J., Li M., Gui B., Fu R., Yao G., Duan Z., Lv Z., Yang Y., Chen Z., Jia L., Tian L. 2015. Activation of AMPK by metformin inhibits TGF-β-induced collagen production in mouse renal fibroblasts. Life Sci. 127, 59–65.

CAS  PubMed  Google Scholar 

Bai X., Zhao G., Chen Q., Li Z., Gao M., Ho W., Xu X., Zhang X.Q. 2022. Inhaled siRNA nanoparticles targeting IL11 inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge. Sci. Adv. 8, eabn7162.

Andugulapati S.B., Gourishetti K., Tirunavalli S.K., Shaikh T.B., Sistla R. 2020. Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-β mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems. Phytomedicine. 78, 153298.

CAS  PubMed  PubMed Central  Google Scholar 

Zhao H., Bian H., Bu X., Zhang S., Zhang P., Yu J., Lai X., Li D., Zhu C., Yao L., Su J. 2016. Targeting of discoidin domain receptor 2 (DDR2) prevents myofibroblast activation and neovessel formation during pulmonary fibrosis. Mol. Ther. 24, 1734–1744.

CAS  PubMed  PubMed Central  Google Scholar 

Yu D., Xiang Y., Gou T., Tong R., Xu C., Chen L., Zhong L., Shi J. 2023. New therapeutic approaches against pulmonary fibrosis. Bioorg. Chem. 138, 106592.

CAS  PubMed  Google Scholar 

Zhang D., Gou Z., Qu Y., Su X. 2024. Understanding how methyltransferase-like 3 functions in lung diseases: From pathogenesis to clinical application. Biomed. Pharmacother. 179, 117421.

CAS  PubMed  Google Scholar 

Su X., Qu Y., Mu D. 2024. Methyltransferase-like 3 modifications of RNAs: Implications for the pathology in the endocrine system. Biochim. Biophys. Acta, Mol. Basis. Dis. 1870, 167010.

CAS  Google Scholar 

Zhang M., Gou Z., Qu Y., Su X. 2024. The indispensability of methyltransferase-like 3 in the immune system: from maintaining homeostasis to driving function. Front. Immunol. 15, 1456891.

CAS  PubMed  PubMed Central  Google Scholar 

Zhang J.X., Huang P.J., Wang D.P., Yang W.Y., Lu J., Zhu Y., Meng X.X., Wu X., Lin Q.H., Lv H., Xie H., Wang R.L. 2021. m(6)A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation. Mol. Ther. 29, 3436–3448.

CAS  PubMed  PubMed Central  Google Scholar 

Wu T., Liu B., Wei Y., Li Z. 2023. TGF-β Regulates m(6)A RNA Methylation after PM(2.5) exposure. Toxics. 11, 1026.

CAS  PubMed  PubMed Central  Google Scholar 

Sun Y., Ge J., Shao F., Ren Z., Huang Z., Ding Z., Dong L., Chen J., Zhang J., Zang Y. 2023. Long noncoding RNA AI662270 promotes kidney fibrosis through enhancing METTL3-mediated m(6) A modification of CTGF mRNA. FASEB J. 37, e23071.

CAS  PubMed  Google Scholar 

Sun Y., Zhang X.C., Li M.D., Bu L.G., Wang B., Li T.Y., Ding N.Z., Ni H. 2023. METTL3 promotes proliferation of goat endometrial epithelial cells by regulating CTGF in an m6A-dependent manner. Biol. Reprod. 108, 902–911.

CAS  PubMed  Google Scholar 

Lu Y., Liu Z., Zhang Y., Wu X., Bian W., Shan S., Yang D., Ren T. 2023. METTL3-mediated m6A RNA methylation induces the differentiation of lung resident mesenchymal stem cells into myofibroblasts via the miR-21/PTEN pathway. Respir. Res. 24, 300.

CAS  PubMed  PubMed Central  Google Scholar 

Wanna-Udom S., Terashima M., Lyu H., Ishimura A., Takino T., Sakari M., Tsukahara T., Suzuki T. 2020. The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB. Biochem. Biophys. Res. Commun. 524, 150–155.

CAS  PubMed  Google Scholar 

Jung H.R., Lee J., Hong S.P., Shin N., Cho A., Shin D.J., Choi J.W., Kim J.I., Lee J.P., Cho S.Y. 2024. Targeting the m(6)A RNA methyltransferase METTL3 attenuates the development of kidney fibrosis. Exp. Mol. Med. 56, 355–369.

CAS  PubMed  PubMed Central  Google Scholar 

Yankova E., Blackaby W., Albertella M., Rak J., De Braekeleer E., Tsagkogeorga G., Pilka E.S., Aspris D., Leggate D., Hendrick A.G., Webster N.A., Andrews B., Fosbeary R., Guest P., Irigoyen N., Eleftheriou M., Gozdecka M., Dias J.M.L., Bannister A.J., Vick B., Jeremias I., Vassiliou G.S., Rausch O., Tzelepis K., Kouzarides T. 2021. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 593, 597–601.

CAS  PubMed  PubMed Central  Google Scholar 

Xiao Y., Yang Y., Hu D. 2021. Knockdown of METTL3 inhibits enterovirus 71-induced apoptosis of mouse Schwann cell through regulation of autophagy. Pathog. Dis. 79, ftab036.

Hickman D.L. 2023. Euthanasia of neonatal rats and mice using carbon monoxide. J. Am. Assoc. Lab. Anim. Sci. 62, 274–278.

PubMed  PubMed Central  Google Scholar 

Vinje M.A., Friedman D.A. 2023. Exogenous spike-in mouse RNAs for accurate differential gene expression analysis in barley using RT-qPCR. Biol. Methods Protoc. 8, bpad034.

Tan M., Liu S., Liu L. 2024. N6-methyladenosine (m6A) RNA modification in fibrosis and collagen-related diseases. Clin. Epigenetics. 16, 127.

CAS  PubMed  PubMed Central  Google Scholar 

Xue T., Qiu X., Liu H., Gan C., Tan Z., Xie Y., Wang Y., Ye T. 2021. Epigenetic regulation in fibrosis progress. Pharmacol. Res. 173,105910.

CAS  PubMed  Google Scholar 

He C., Ji Y., Zhang Y., Ou J., Wu D., Qin H., Hua J., Li Q., Zheng H. 2025. Inhibition of Mettl3 by STM2457 and loss of macrophage Mettl3 alleviate pulmonary hypertension and right heart remodeling. Lung. 203, 34.

CAS  PubMed  Google Scholar 

Bolívar S., Pérez-Cantillo M., Monterroza-Torres J., Vásquez-Trincado C., Castellar-Lopez J., Mendoza-Torres E. 2023. The Role of METTL3 in the progression of cardiac fibrosis. Curr. Top. Med. Chem. 23, 2427–2435.

PubMed  Google Scholar 

Li T., Zhuang Y., Yang W., Xie Y., Shang W., Su S., Dong X., Wu J., Jiang W., Zhou Y., Li Y., Zhou X., Zhang M., Lu Y., Pan Z. 2021.Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts. FASEB J. 35, e21162.

CAS  PubMed  Google Scholar 

Isshiki T., Naiel S., Vierhout M., Otsubo K., Ali P., Tsubouchi K., Yazdanshenas P., Kumaran V., Dvorkin-Gheva A., Kolb M.R.J., Ask K. 2024.Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases. Pharmacol. Ther. 253,108578.

CAS  PubMed  Google Scholar 

Yanagihara T., Tsubouchi K., Gholiof M., Chong S.G., Lipson K.E., Zhou Q., Scallan C., Upagupta C., Tikkanen J., Keshavjee S., Ask K., Kolb M.R.J. 2022. Connective-tissue growth factor contributes to TGF-β1-induced lung fibrosis. Am. J. Respir. Cell Mol. Biol. 66, 260–270.

CAS  PubMed  Google Scholar 

Kasam R.K., Ghandikota S., Soundararajan D., Reddy G.B., Huang S.K., Jegga A.G., Madala S.K. 2020. Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis. EMBO Mol. Med. 12, e12131.

CAS  PubMed  PubMed Central  Google Scholar 

Richeldi L., Collard H.R., Jones M.G. 2017. Idiopathic pulmonary fibrosis. Lancet. 389, 1941–1952.

PubMed  Google Scholar 

Marcoux V., Lok S.D., Mondal P., Assayag D., Fisher J.H., Shapera S., Morisset J., Manganas H., Fell C.D., Hambly N., Cox P.G., Kolb M., Gershon A.S., To T., Sadatsafavi M., Khalil N., Wong A.W., Wilcox P.G., Ryerson C.J., Vu T., Johannson K.A. 2024. Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort. Respirology. 29, 596–604.

PubMed  Google Scholar 

Comments (0)

No login
gif