METTL3-mediated m6A RNA methylation induces the differentiation of lung resident mesenchymal stem cells into myofibroblasts via the miR-21/PTEN pathway

Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G. Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res. 2021;22(1):109.

Article  PubMed  PubMed Central  Google Scholar 

Moss BJ, Ryter SW, Rosas IO. Pathogenic mechanisms underlying idiopathic pulmonary fibrosis. Annu Rev Pathol. 2022;17:515–46.

Article  CAS  PubMed  Google Scholar 

Kolb M, Bonella F, Wollin L. Therapeutic targets in idiopathic pulmonary fibrosis. Respir Med. 2017;131:49–57.

Article  PubMed  Google Scholar 

Spagnolo P, Kropski JA, Jones MG, Lee JS, Rossi G, Karampitsakos T, Maher TM, Tzouvelekis A, Ryerson CJ. Idiopathic pulmonary fibrosis: disease mechanisms and drug development. Pharmacol Ther. 2021;222:107798.

Article  CAS  PubMed  Google Scholar 

da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119(Pt 11):2204–13.

Article  PubMed  Google Scholar 

Jun D, Garat C, West J, Thorn N, Chow K, Cleaver T, Sullivan T, Torchia EC, Childs C, Shade T, Tadjali M, Lara A, Nozik-Grayck E, Malkoski S, Sorrentino B, Meyrick B, Klemm D, Rojas M, Wagner DH Jr, Majka SM. The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation. Stem Cells. 2011;29(4):725–35.

Article  PubMed  Google Scholar 

Horie S, Masterson C, Devaney J, Laffey JG. Stem cell therapy for acute respiratory distress syndrome: a promising future? Curr Opin Crit Care. 2016;22(1):14–20.

Article  PubMed  Google Scholar 

Sabatini F, Petecchia L, Tavian M, de Jordon Villeroche V, Rossi GA, Brouty-Boye D. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest. 2005;85(8):962–71.

Article  CAS  PubMed  Google Scholar 

Wang Y, Lu Y, Wu Y, Sun Y, Zhou Y, Ma Q, Zheng Y, Yu Q, Cao Y, Chen G, Zhang T, Dai X, Ren T, Ma Y, Zuo W. Alveolar differentiation potency of human distal airway stem cells is associated with pulmonary pathological conditions. Stem Cells Int. 2019;2019:7123078.

Article  PubMed  PubMed Central  Google Scholar 

Lu Y, Zhang T, Shan S, Wang S, Bian W, Ren T, Yang D. MiR-124 regulates transforming growth factor-beta1 induced differentiation of lung resident mesenchymal stem cells to myofibroblast by repressing Wnt/beta-catenin signaling. Dev Biol. 2019;449(2):115–21.

Article  CAS  PubMed  Google Scholar 

Badri L, Murray S, Liu LX, Walker NM, Flint A, Wadhwa A, Chan KM, Toews GB, Pinsky DJ, Martinez FJ, Lama VN. Mesenchymal stromal cells in bronchoalveolar lavage as predictors of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2011;183(8):1062–70.

Article  PubMed  Google Scholar 

Bentley JK, Popova AP, Bozyk PD, Linn MJ, Baek AE, Lei J, Goldsmith AM, Hershenson MB. Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype. Respir Res. 2010;11:127.

Article  PubMed  PubMed Central  Google Scholar 

Chandola U, Das R, Panda B. Role of the N6-methyladenosine RNA mark in gene regulation and its implications on development and disease. Brief Funct Genomics. 2015;14(3):169–79.

Article  CAS  PubMed  Google Scholar 

Dominissini D, Moshitch-Moshkovitz S, Salmon-Divon M, Amariglio N, Rechavi G. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing. Nat Protoc. 2013;8(1):176–89.

Article  CAS  PubMed  Google Scholar 

Maity A, Das B. N6-methyladenosine modification in mRNA: machinery, function and implications for health and diseases. FEBS J. 2016;283(9):1607–30.

Article  CAS  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. Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts. FASEB J. 2021;35(2):e21162.

Article  CAS  PubMed  Google Scholar 

Xing J, He YC, Wang KY, Wan PZ, Zhai XY. Involvement of YTHDF1 in renal fibrosis progression via up-regulating YAP. Faseb j. 2022;36(2):e22144.

Article  CAS  PubMed  Google Scholar 

Wang J, Du M, Meng L, Yang Y, He S, Zhu Y, Ren X, Wei M, Dong R, Zheng S, Chen G. Integrative analysis implicates the significance of m6A in the liver fibrosis of biliary atresia by regulating THY1. Hepatol Commun. 2023;7(1):e0004.

Article  PubMed  PubMed Central  Google Scholar 

Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, Deng X, Wang Y, Weng X, Hu C, Yu M, Skibbe J, Dai Q, Zou D, Wu T, Yu K, Weng H, Huang H, Ferchen K, Qin X, Zhang B, Qi J, Sasaki AT, Plas DR, Bradner JE, Wei M, Marcucci G, Jiang X, Mulloy JC, Jin J, He C, Chen J. R-2HG exhibits anti-tumor activity by targeting FTO/m(6)A/MYC/CEBPA signaling. Cell. 2018;172(1–2):90-105.e23.

Article  CAS  PubMed  Google Scholar 

Erson-Bensan AE, Begik O. m6A Modification and Implications for microRNAs. Microrna. 2017;6(2):97–101.

Article  CAS  PubMed  Google Scholar 

Alarcón CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015;519(7544):482–5.

Article  PubMed  PubMed Central  Google Scholar 

Kölling M, Kaucsar T, Schauerte C, Hübner A, Dettling A, Park JK, Busch M, Wulff X, Meier M, Scherf K, Bukosza N, Szénási G, Godó M, Sharma A, Heuser M, Hamar P, Bang C, Haller H, Thum T, Lorenzen JM. Therapeutic miR-21 silencing ameliorates diabetic kidney disease in mice. Mol Ther. 2017;25(1):165–80.

Article  PubMed  PubMed Central  Google Scholar 

Wang Z, Zhou H, Cheng F, Zhang Z, Long S. MiR-21 regulates epithelial-mesenchymal transition in intestinal fibrosis of Crohn’s disease by targeting PTEN/mTOR. Dig Liver Dis. 2022;54(10):1358–66.

Article  CAS  PubMed  Google Scholar 

Nonaka CKV, Sampaio GL, Silva KN, Khouri R, Macedo CT, Chagas Translational Research Consortium, Rogatto SR, Dos Ribeiro Santos R, Souza BSF, Soares MBP. Therapeutic miR-21 silencing reduces cardiac fibrosis and modulates inflammatory response in chronic Chagas disease. Int J Mol Sci. 2021;22(7):3307.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis. Transl Res. 2011;157(4):191–9.

Article  CAS  PubMed  Google Scholar 

Jiang X, Liu B, Nie Z, Duan L, Xiong Q, Jin Z, Yang C, Chen Y. The role of m6A modification in the biological functions and diseases. Signal Transduct Target Ther. 2021;6(1):74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Doherty DF, Roets L, Krasnodembskaya AD. The role of lung resident mesenchymal stromal cells in the pathogenesis and repair of chronic lung disease. Stem Cells. 2023;41(5):431–43.

Article  PubMed  PubMed Central  Google Scholar 

Gong X, Sun Z, Cui D, Xu X, Zhu H, Wang L, Qian W, Han X. Isolation and characterization of lung resident mesenchymal stem cells capable of differentiating into alveolar epithelial type II cells. Cell Biol Int. 2014;38(4):405–11.

Article  CAS  PubMed  Google Scholar 

Jones E, McGonagle D. Human bone marrow mesenchymal stem cells in vivo. Rheumatology. 2008;47(2):126–31.

Article  CAS  PubMed  Google Scholar 

Tzouvelekis A, Koliakos G, Ntolios P, Baira I, Bouros E, Oikonomou A, Zissimopoulos A, Kolios G, Kakagia D, Paspaliaris V, Kotsianidis I, Froudarakis M, Bouros D. Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal. J Transl Med. 2011;9:182.

Article  PubMed  PubMed Central  Google Scholar 

Bagnato G, Harari S. Cellular interactions in the pathogenesis of interstitial lung diseases. Eur Respir Rev. 2015;24(135):102–14.

Article  PubMed  PubMed Central  Google Scholar 

Papaioannou O, Karampitsakos T, Barbayianni I, Chrysikos S, Xylourgidis N, Tzilas V, Bouros D, Aidinis V, Tzouvelekis A. Metabolic disorders in chronic lung diseases. Front Med. 2017;4:246.

Article  Google Scholar 

Popova AP, Bozyk PD, Bentley JK, Linn MJ, Goldsmith AM, Schumacher RE, Weiner GM, Filbrun AG, Hershenson MB. Isolation of tracheal aspirate mesenchymal stromal cells predicts bronchopulmonary dysplasia. Pediatrics. 2010;126(5):e1127–33.

Article  PubMed  Google Scholar 

Walker N, Badri L, Wettlaufer S, Flint A, Sajjan U, Krebsbach PH, Keshamouni VG, Peters-Golden M, Lama VN. Resident tissue-specific mesenchymal progenitor cells contribute to fibrogenesis in human lung allografts. Am J Pathol. 2011;178(6):2461–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weisser K, Ganz R, Olafsson A, Wyler F, Rutishauser M. Bronchopulmonary dysplasia in the premature baby. Respiration. 1970;27(Suppl):36–40.

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