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Inflammation plays a critical role in the progression of pulmonary fibrosis. Thymosin β4 (Tβ4) has antioxidant, anti-inflammatory, and antifibrotic effects. Although the potent protective role of Tβ4 in bleomycin-induced pulmonary fibrosis has been validated, the underlying mechanism is not clear; moreover, the influence of Tβ4 on lipopolysaccharide (LPS)-induced lung injury/fibrosis has not been reported. Expression of Tβ4 in fibrotic lung tissues was assessed by real-time quantitative reverse-transcription PCR (rt-PCR), immunohistochemistry (IHC), and western blotting. The effects of intraperitoneal adeno-associated virus-Tβ4 (AAV-Tβ4) on LPS-induced lung injury and fibrosis were observed through the evaluation of collagen deposition and α-smooth muscle actin (SMA) expression. In vitro tests with HPAEpiC and HLF-1 cells were performed to confirm the effects of Tβ4. In this study, we evaluated the role of Tβ4 in pulmonary fibrosis and explored the possible underlying mechanisms. Tβ4 was markedly upregulated in human or mouse fibrotic lung tissues. AAV-Tβ4 markedly alleviated LPS-induced oxidative damage, lung injury, inflammation, and fibrosis in mice. Our in vitro experiments also showed that LPS inhibited mitophagy and promoted inflammation via oxidative stress in HPAEpiC, and Tβ4 significantly attenuated LPS-induced mitophagy inhibition, inflammasome activation, and transforming growth factor-β (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in HPAEpiC. Moreover, Tβ4 suppressed the proliferation and attenuated the TGF-β1-induced activation of HLF-1 cells. In conclusion, Tβ4 alleviates LPS-induced lung injury, inflammation, and subsequent fibrosis in mice, suggesting that Tβ4 has a protective role in the pathogenesis of pulmonary fibrosis. Tβ4 is involved in attenuating oxidative injury, promoting mitophagy, and alleviating inflammation and fibrosis. Modulation of Tβ4 might be a novel strategy for treating pulmonary fibrosis.

Titel:	Thymosin β4 Suppresses LPS-Induced Murine Lung Fibrosis by Attenuating Oxidative Injury and Alleviating Inflammation.
Autor/in / Beteiligte Person:	Tian, Z ; Yao, N ; Wang, F ; Ruan, L
Link:	Full Text Finder (Volltext)
Zeitschrift:	Inflammation, Jg. 45 (2022-02-01), Heft 1, S. 59-73
Veröffentlichung:	1999- : New York, NY : Kluwer Academic/Plenum Publishers ; <i>Original Publication</i>: New York, Plenum Press., 2022
Medientyp:	academicJournal
ISSN:	1573-2576 (electronic)
DOI:	10.1007/s10753-021-01528-6
Schlagwort:	Animals Humans Lipopolysaccharides Male Mice Mice, Inbred ICR Pulmonary Fibrosis etiology Inflammation metabolism Mitophagy physiology Oxidative Stress physiology Pulmonary Fibrosis metabolism Thymosin metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Inflammation] 2022 Feb; Vol. 45 (1), pp. 59-73. <i>Date of Electronic Publication: </i>2021 Aug 19. MeSH Terms: Inflammation / metabolism ; Mitophagy / physiology ; Oxidative Stress / physiology ; Pulmonary Fibrosis / metabolism ; Thymosin / *metabolism ; Animals ; Humans ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred ICR ; Pulmonary Fibrosis / etiology References: Sgalla, G., B. Iovene, M. Calvello, M. Ori, F. Varone, and L. Richeldi. 2018. Idiopathic pulmonary fibrosis: Pathogenesis and management. Respiratory research 19: 32. (PMID: 10.1186/s12931-018-0730-2) ; Wang, K., Q. Ju, J. Cao, W. Tang, and J. Zhang. 2017. Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis: a systematic review and meta-analysis. Medicine 96: e7083. ; Wolters, P.J., H.R. Collard, and K.D. Jones. 2014. Pathogenesis of idiopathic pulmonary fibrosis. Annual review of pathology 9: 157–179. (PMID: 10.1146/annurev-pathol-012513-104706) ; Fois, A.G., E. Sotgiu, V. Scano, S. Negri, S. Mellino, E. Zinellu, P. Pirina, G. Pintus, C. Carru, A.A. Mangoni, and A. Zinellu. 2020. Effects of pirfenidone and nintedanib on markers of systemic oxidative stress and inflammation in patients with idiopathic pulmonary fibrosis: a preliminary report. Antioxidants9 . ; Oldham, J.M., S.F. Ma, F.J. Martinez, K.J. Anstrom, G. Raghu, D.A. Schwartz, E. Valenzi, L. Witt, C. Lee, R. Vij, Y. Huang, M.E. Strek, and I. Noth. 2015. TOLLIP, MUC5B, and the response to N-acetylcysteine among individuals with idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine 192: 1475–1482. (PMID: 10.1164/rccm.201505-1010OC) ; Laporta, H.R., P.M. Aguilar, C.M.T. Lázaro, and G.P. Ussetti. 2018. Lung transplantation in idiopathic pulmonary fibrosis. Medical sciences 6. ; Mannherz, H.G., and E. Hannappel. 2009. The beta-thymosins: Intracellular and extracellular activities of a versatile actin binding protein family. Cell motility and the cytoskeleton 66: 839–851. (PMID: 10.1002/cm.20371) ; Jin, R., Y. Li, L. Li, D.H. Kim, C.D. Yang, H.S. Son, J.H. Choi, H.J. Yoon, and K.C. Yoon. 2020. Anti-inflammatory effects of glycine thymosin β4 eye drops in experimental dry eye. Biomedical reports 12: 319–325. (PMID: 323824167201140) ; Han, T., Y. Liu, H. Liu, Z.Y. Zhu, Y. Li, S.X. Xiao, Z. Guo, and Z.G. Zhao. 2010. Serum thymosin beta4 levels in patients with hepatitis B virus-related liver failure. World journal of gastroenterology 16: 625–630. (PMID: 10.3748/wjg.v16.i5.625) ; Conte, E., E. Fagone, E. Gili, M. Fruciano, M. Iemmolo, M.P. Pistorio, D. Impellizzeri, M. Cordaro, S. Cuzzocrea, and C. Vancheri. 2016. Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis. Oncotarget 7: 33841–33854. (PMID: 10.18632/oncotarget.8409) ; Shah, R., K. Reyes-Gordillo, Y. Cheng, R. Varatharajalu, J. Ibrahim, and M.R. Lakshman. 2018. Thymosin β4 prevents oxidative stress, inflammation, and fibrosis in ethanol- and LPS-induced liver injury in mice. Oxidative medicine and cellular longevity 2018: 9630175. (PMID: 10.1155/2018/9630175) ; De Santis, M., R. Inzitari, S.L. Bosello, G. Peluso, C. Fanali, F. Iavarone, G. Zizzo, M. Bocci, T. Cabras, I. Messana, L. Fuso, F. Varone, G. Pagliari, M. Castagnola, and G. Ferraccioli. 2011. β-Thymosins and interstitial lung disease: Study of a scleroderma cohort with a one-year follow-up. Respiratory research 12: 22. (PMID: 10.1186/1465-9921-12-22) ; Levine, B., and G. Kroemer. 2008. Autophagy in the pathogenesis of disease. Cell 132: 27–42. (PMID: 10.1016/j.cell.2007.12.018) ; Lazarou, M., D.A. Sliter, L.A. Kane, S.A. Sarraf, C. Wang, J.L. Burman, D.P. Sideris, A.I. Fogel, and R.J. Youle. 2015. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524: 309–314. (PMID: 10.1038/nature14893) ; Sorbara, M.T., and S.E. Girardin. 2011. Mitochondrial ROS fuel the inflammasome. Cell research 21: 558–560. (PMID: 10.1038/cr.2011.20) ; Renga, G., V. Oikonomou, S. Moretti, C. Stincardini, M.M. Bellet, M. Pariano, A. Bartoli, S. Brancorsini, P. Mosci, A. Finocchi, P. Rossi, C. Costantini, E. Garaci, A.L. Goldstein, and L. Romani. 2019. Thymosin β4 promotes autophagy and repair via HIF-1α stabilization in chronic granulomatous disease. Life science alliance 2. ; Kumar, S., and S. Gupta. 2011. Thymosin beta 4 prevents oxidative stress by targeting antioxidant and anti-apoptotic genes in cardiac fibroblasts. PloS one 6: e26912. ; Suzuki, T., Y. Tada, S. Gladson, R. Nishimura, I. Shimomura, S. Karasawa, K. Tatsumi, and J. West. 2017. Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition. Respiratory research 18: 177. (PMID: 10.1186/s12931-017-0660-4) ; Yuan, J., Y. Shen, X. Yang, Y. Xie, X. Lin, W. Zeng, Y. Zhao, M. Tian, and Y. Zha. 2017. Thymosin β4 alleviates renal fibrosis and tubular cell apoptosis through TGF-β pathway inhibition in UUO rat models. BMC nephrology 18: 314. (PMID: 10.1186/s12882-017-0708-1) ; Peng, H., J. Xu, X.P. Yang, X. Dai, E.L. Peterson, O.A. Carretero, and N.E. Rhaleb. 2014. Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction. American journal of physiology. Heart and circulatory physiology 307: H741-751. (PMID: 10.1152/ajpheart.00129.2014) ; Liu, M.H., A.H. Lin, H.F. Lee, H.K. Ko, T.S. Lee, and Y.R. Kou. 2014. Paeonol attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling. Mediators of inflammation 2014:651890. ; Li, F., M. Xu, M. Wang, L. Wang, H. Wang, H. Zhang, Y. Chen, J. Gong, J.J. Zhang, I.M. Adcock, K.F. Chung, and X. Zhou. 2018. Roles of mitochondrial ROS and NLRP3 inflammasome in multiple ozone-induced lung inflammation and emphysema. Respiratory research 19: 230. (PMID: 10.1186/s12931-018-0931-8) ; Downs, C.A., N.M. Johnson, G. Tsaprailis, and M.N. Helms. 2018. RAGE-induced changes in the proteome of alveolar epithelial cells. Journal of proteomics 177: 11–20. (PMID: 10.1016/j.jprot.2018.02.010) ; Basit, F., van Oppen LM, L. Schöckel, H.M. Bossenbroek, van Emst-de Vries SE, J.C. Hermeling, S. Grefte, C. Kopitz, M. Heroult, W.P. Hgm, and W.J. Koopman. 2017. Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell death & disease 8:e2716. ; O’Dwyer, D.N., S.L. Ashley, S.J. Gurczynski, M. Xia, C. Wilke, N.R. Falkowski, K.C. Norman, K.B. Arnold, G.B. Huffnagle, M.L. Salisbury, M.K. Han, K.R. Flaherty, E.S. White, F.J. Martinez, J.R. Erb-Downward, S. Murray, B.B. Moore, and R.P. Dickson. 2019. Lung microbiota contribute to pulmonary inflammation and disease progression in pulmonary fibrosis. American journal of respiratory and critical care medicine 199: 1127–1138. (PMID: 10.1164/rccm.201809-1650OC) Contributed Indexing: Keywords: Adeno-associated virus; Mitophagy.; Oxidative stress; Pulmonary fibrosis; Thymosin β4 Substance Nomenclature: 0 (Lipopolysaccharides) ; 549LM7U24W (thymosin beta(4)) ; 61512-21-8 (Thymosin) Entry Date(s): Date Created: 20210820 Date Completed: 20220324 Latest Revision: 20220324 Update Code: 20231215

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Thymosin β4 Suppresses LPS-Induced Murine Lung Fibrosis by Attenuating Oxidative Injury and Alleviating Inflammation.