Studies on the Anti-Pulmonary Fibrotic Effect of FGF-2-Targeting Binding Peptide G8

Peiji Lan; Yuan Wang; Wei Li; Ju Wang*

Peiji Lan, Yuan Wang, Wei Li and Ju Wang*

Volume3-Issue7
Dates: Received: 2022-07-18 | Accepted: 2022-07-29 | Published: 2022-07-30
Pages: 819-826

Abstract

In our previous research, all the data showed that FGF-2 was very possible to be a new target for inhibiting lung fibrosis. Therefore, we plan to find the specific and small peptides to block FGF-2 signaling, hoping to develop a new scheme to treat pulmonary fibrosis better than FGF.

Receptor extracellular domain. As a result, we biopanned several peptides through phage display technology, and finally got G8 which is the strongest peptide binding to FGF-2. Studies have found that G8 is almost non-toxic to L929 mouse lung fibroblast cells. In mouse bleomycin-induced pulmonary fibrosis model, the lung coefficient of the rats decreased significantly after 30 days of G8 treatment, the ground glass shadow decreases in CT scan, also the collagen deposition was alleviated dramatically (Masson staining), which suggests that the pulmonary fibrosis has been inhibited dramatically. And all above results are better than Pirfenidone (PFD) treatment group. The studies suggests obviously that G8 antagonizes the promoting effect of FGF-2 in the lung fibrotic process, which has a predictable applicating prospect.

FullText HTML FullText PDF DOI: 10.37871/jbres1518

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How to cite this article

Lan P, Wang Y, Li W, Wang J. Studies on the Anti-Pulmonary Fibrotic Effect of FGF-2-Targeting Binding Peptide G8. J Biomed Res Environ Sci. 2022 July 30; 3(7): 819-826. doi: 10.37871/jbres1518, Article ID: JBRES1518, Available at: https://www.jelsciences.com/articles/jbres1518.pdf

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References

Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otaola M, Skowasch D, Park JS, Poonyagariyagorn HK, Wuyts W, Wells AU. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018 Dec 21;27(150):180076. doi: 10.1183/16000617.0076-2018. PMID: 30578335.
Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018 May 10;378(19):1811-1823. doi: 10.1056/NEJMra1705751. PMID: 29742380.
Lee HE, Myong JP, Kim HR, Rhee CK, Yoon HK, Koo JW. Incidence and prevalence of idiopathic interstitial pneumonia and idiopathic pulmonary fibrosis in Korea. Int J Tuberc Lung Dis. 2016 Jul;20(7):978-84. doi: 10.5588/ijtld.16.0003. PMID: 27287654.
Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J Clin Med. 2018 Aug 6;7(8):201. doi: 10.3390/jcm7080201. PMID: 30082599; PMCID: PMC6111543.
Sathiyamoorthy G, Sehgal S, Ashton RW. Pirfenidone and Nintedanib for Treatment of Idiopathic Pulmonary Fibrosis. South Med J. 2017 Jun;110(6):393-398. doi: 10.14423/SMJ.0000000000000655. PMID: 28575896.
Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, Richeldi L, Kolb M, Tetzlaff K, Stowasser S, Coeck C, Clerisme-Beaty E, Rosenstock B, Quaresma M, Haeufel T, Goeldner RG, Schlenker-Herceg R, Brown KK; INBUILD Trial Investigators. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019 Oct 31;381(18):1718-1727. doi: 10.1056/NEJMoa1908681. Epub 2019 Sep 29. PMID: 31566307.
Rogliani P, Calzetta L, Cavalli F, Matera MG, Cazzola M. Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Pulm Pharmacol Ther. 2016 Oct;40:95-103. doi: 10.1016/j.pupt.2016.07.009. Epub 2016 Jul 29. PMID: 27481628.
Jin J, Togo S, Kadoya K, Tulafu M, Namba Y, Iwai M, Watanabe J, Nagahama K, Okabe T, Hidayat M, Kodama Y, Kitamura H, Ogura T, Kitamura N, Ikeo K, Sasaki S, Tominaga S, Takahashi K. Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-β1. Respir Res. 2019 Jun 11;20(1):119. doi: 10.1186/s12931-019-1093-z. PMID: 31185973; PMCID: PMC6558902.
Moor CC, Mostard RLM, Grutters JC, Bresser P, Aerts JGJV, Dirksen CD, Kimman ML, Wijsenbeek MS. Patient expectations, experiences and satisfaction with nintedanib and pirfenidone in idiopathic pulmonary fibrosis: a quantitative study. Respir Res. 2020 Jul 23;21(1):196. doi: 10.1186/s12931-020-01458-1. PMID: 32703201; PMCID: PMC7376884.
Hui Q, Jin Z, Li X, Liu C, Wang X. FGF Family: From Drug Development to Clinical Application. Int J Mol Sci. 2018 Jun 26;19(7):1875. doi: 10.3390/ijms19071875. PMID: 29949887; PMCID: PMC6073187.
Prudovsky I. Cellular Mechanisms of FGF-Stimulated Tissue Repair. Cells. 2021 Jul 20;10(7):1830. doi: 10.3390/cells10071830. PMID: 34360000; PMCID: PMC8304273.
Ghedini GC, Ronca R, Presta M, Giacomini A. Future applications of FGF/FGFR inhibitors in cancer. Expert Rev Anticancer Ther. 2018 Sep;18(9):861-872. doi: 10.1080/14737140.2018.1491795. Epub 2018 Jul 2. PMID: 29936878.
Epstein Shochet G, Brook E, Bardenstein-Wald B, Shitrit D. TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling. Respir Res. 2020 Feb 18;21(1):56. doi: 10.1186/s12931-020-1319-0. PMID: 32070329; PMCID: PMC7029598.
Yanagihara T, Sato S, Upagupta C, Kolb M. What have we learned from basic science studies on idiopathic pulmonary fibrosis? Eur Respir Rev. 2019 Sep 11;28(153):190029. doi: 10.1183/16000617.0029-2019. PMID: 31511255.
Yu ZH, Wang DD, Zhou ZY, He SL, Chen AA, Wang J. Mutant soluble ectodomain of fibroblast growth factor receptor-2 IIIc attenuates bleomycin-induced pulmonary fibrosis in mice. Biol Pharm Bull. 2012;35(5):731-6. doi: 10.1248/bpb.35.731. PMID: 22687409.
Ju W, Zhihong Y, Zhiyou Z, Qin H, Dingding W, Li S, Baowei Z, Xing W, Ying H, An H. Inhibition of α-SMA by the ectodomain of FGFR2c attenuates lung fibrosis. Mol Med. 2012 Sep 7;18(1):992-1002. doi: 10.2119/molmed.2011.00425. PMID: 22451267; PMCID: PMC3459475.
El-Baz LMF, Shoukry NM, Hafez HS, Guzy RD, Salem ML. Fibroblast Growth Factor 2 Augments Transforming Growth Factor Beta 1 Induced Epithelial-mesenchymal Transition in Lung Cell Culture Model. Iran J Allergy Asthma Immunol. 2020 Aug 25;19(4):348-361. doi: 10.18502/ijaai.v19i4.4110. PMID: 33463102; PMCID: PMC8366022.
Guzy RD, Li L, Smith C, Dorry SJ, Koo HY, Chen L, Ornitz DM. Pulmonary fibrosis requires cell-autonomous mesenchymal fibroblast growth factor (FGF) signaling. J Biol Chem. 2017 Jun 23;292(25):10364-10378. doi: 10.1074/jbc.M117.791764. Epub 2017 May 9. PMID: 28487375; PMCID: PMC5481550.
Jieming G, Liu C, Yang Y, Mo S, Yang X, Wang J. Inhibitory effects of msFGFR2c on the epithelial-to-mesenchymal transition of AE2 cells in pulmonary fibrosis. Biotechnol Lett. 2020 Jun;42(6):1061-1070. doi: 10.1007/s10529-020-02852-x. Epub 2020 Mar 4. PMID: 32130565; PMCID: PMC7211205.
Jeong DE, Lee Y, Lee SV. Western Blot Analysis of C. elegans Proteins. Methods Mol Biol. 2018;1742:213-225. doi: 10.1007/978-1-4939-7665-2_19. PMID: 29330803.
Hansford KA, Ziora ZM, Cooper MA, Blaskovich MAT. Solid-Phase Synthesis of Octapeptin Lipopeptides. Methods Mol Biol. 2020;2103:199-213. doi: 10.1007/978-1-0716-0227-0_13. PMID: 31879927.
Raghu G, Chen SY, Hou Q, Yeh WS, Collard HR. Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18-64 years old. Eur Respir J. 2016 Jul;48(1):179-86. doi: 10.1183/13993003.01653-2015. Epub 2016 Apr 28. PMID: 27126689.
Nagaraja SS, Nagarajan D. Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators. Curr Drug Targets. 2018;19(10):1191-1204. doi: 10.2174/1389450119666180207092234. PMID: 29412104.
Veres-Székely A, Pap D, Sziksz E, Jávorszky E, Rokonay R, Lippai R, Tory K, Fekete A, Tulassay T, Szabó AJ, Vannay Á. Selective measurement of α smooth muscle actin: why β-actin can not be used as a housekeeping gene when tissue fibrosis occurs. BMC Mol Biol. 2017 Apr 27;18(1):12. doi: 10.1186/s12867-017-0089-9. PMID: 28449660; PMCID: PMC5408491.
Meyer KC. Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis. Expert Rev Respir Med. 2017 May;11(5):343-359. doi: 10.1080/17476348.2017.1312346. Epub 2017 Apr 10. PMID: 28345383.
Justet A, Klay D, Porcher R, Cottin V, Ahmad K, Molina Molina M, Nunes H, Reynaud-Gaubert M, Naccache JM, Manali E, Froidure A, Jouneau S, Wemeau L, Andrejak C, Gondouin A, Hirschi S, Blanchard E, Bondue B, Bonniaud P, Tromeur C, Prévot G, Marchand-Adam S, Funke-Chambour M, Gamez AS, Ba I, Papiris S, Grutters J, Crestani B, van Moorsel C, Kannengiesser C, Borie R; OrphaLung Network. Safety and efficacy of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis and carrying a telomere-related gene mutation. Eur Respir J. 2021 Feb 11;57(2):2003198. doi: 10.1183/13993003.03198-2020. PMID: 33214205.