YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis
Abstract
:1. Introduction
2. YAP/TAZ–TEAD Biology and Signaling Mechanism
3. YAP/TAZ Signaling Pathway in PF
4. Targeting the YAP/TAZ Signaling Cascade in PF
5. Future Perspectives—Outlook
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Wuyts, W.A.; Agostini, C.; Antoniou, K.M.; Bouros, D.; Chambers, R.C.; Cottin, V.; Egan, J.J.; Lambrecht, B.N.; Lories, R.; Parfrey, H.; et al. The Pathogenesis of Pulmonary Fibrosis: A Moving Target. Eur. Respir. J. 2013, 41, 1207–1218. [Google Scholar] [CrossRef] [PubMed]
- Wilson, M.S.; Wynn, T.A. Pulmonary Fibrosis: Pathogenesis, Etiology and Regulation. Mucosal Immunol. 2009, 2, 103–121. [Google Scholar] [CrossRef] [PubMed]
- Mei, Q.; Liu, Z.; Zuo, H.; Yang, Z.; Qu, J. Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis. Front. Pharmacol. 2022, 12, 797292. [Google Scholar] [CrossRef]
- Fujimoto, H.; Kobayashi, T.; Azuma, A. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis. Clin. Med. Insights Circ. Respir. Pulm. Med. 2015, 9, 179–185. [Google Scholar] [CrossRef]
- American Cancer Society. Lung Cancer Survival Rates. 2024. Available online: https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/survival-rates.html (accessed on 9 July 2024).
- Tsubouchi, K.; Hamada, N.; Tokunaga, S.; Ichiki, K.; Takata, S.; Ishii, H.; Kitasato, Y.; Okamoto, M.; Kawakami, S.; Yatera, K.; et al. Survival and Acute Exacerbation for Patients with Idiopathic Pulmonary Fibrosis (IPF) or Non-IPF Idiopathic Interstitial Pneumonias: 5-Year Follow-up Analysis of a Prospective Multi-Institutional Patient Registry. BMJ Open Respir. Res. 2023, 10, e001864. [Google Scholar] [CrossRef]
- Nathan, S.D.; Shlobin, O.A.; Weir, N.; Ahmad, S.; Kaldjob, J.M.; Battle, E.; Sheridan, M.J.; du Bois, R.M. Long-Term Course and Prognosis of Idiopathic Pulmonary Fibrosis in the New Millennium. Chest 2011, 140, 221–229. [Google Scholar] [CrossRef] [PubMed]
- Ley, B.; Ryerson, C.J.; Vittinghoff, E.; Ryu, J.H.; Tomassetti, S.; Lee, J.S.; Poletti, V.; Buccioli, M.; Elicker, B.M.; Jones, K.D.; et al. A Multidimensional Index and Staging System for Idiopathic Pulmonary Fibrosis. Ann. Intern. Med. 2012, 156, 684–691. [Google Scholar] [CrossRef]
- Wilson, K.C.; Raghu, G. The 2015 Guidelines for Idiopathic Pulmonary Fibrosis: An Important Chapter in the Evolution of the Management of Patients with IPF. Eur. Respir. J. 2015, 46, 883–886. [Google Scholar] [CrossRef]
- Van Den Hoogen, L.L.; Van Laar, J.M. Targeted Therapies in Systemic Sclerosis, Myositis, Antiphospholipid Syndrome, and Sjögren’s Syndrome. Best Pract. Res. Clin. Rheumatol. 2020, 34, 101485. [Google Scholar] [CrossRef]
- Aimo, A.; Spitaleri, G.; Nieri, D.; Tavanti, L.M.; Meschi, C.; Panichella, G.; Lupón, J.; Pistelli, F.; Carrozzi, L.; Bayes-Genis, A.; et al. Pirfenidone for Idiopathic Pulmonary Fibrosis and Beyond. Card. Fail. Rev. 2022, 8, e12. [Google Scholar] [CrossRef]
- Proesmans, V.L.J.; Drent, M.; Elfferich, M.D.P.; Wijnen, P.A.H.M.; Jessurun, N.T.; Bast, A. Self-Reported Gastrointestinal Side Effects of Antifibrotic Drugs in Dutch Idiopathic Pulmonary Fibrosis Patients. Lung 2019, 197, 551–558. [Google Scholar] [CrossRef] [PubMed]
- Man, R.K.; Gogikar, A.; Nanda, A.; Janga, L.S.N.; Sambe, H.G.; Yasir, M.; Ramphall, S. A Comparison of the Effectiveness of Nintedanib and Pirfenidone in Treating Idiopathic Pulmonary Fibrosis: A Systematic Review. Cureus 2024, 16, e54268. [Google Scholar] [CrossRef] [PubMed]
- Chianese, M.; Screm, G.; Salton, F.; Confalonieri, P.; Trotta, L.; Barbieri, M.; Ruggero, L.; Mari, M.; Reccardini, N.; Geri, P.; et al. Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows. Pharmaceuticals 2024, 17, 709. [Google Scholar] [CrossRef] [PubMed]
- Laporta Hernandez, R.; Aguilar Perez, M.; Lázaro Carrasco, M.T.; Ussetti Gil, P. Lung Transplantation in Idiopathic Pulmonary Fibrosis. Med. Sci. 2018, 6, 68. [Google Scholar] [CrossRef] [PubMed]
- Mia, M.M.; Singh, M.K. New Insights into Hippo/YAP Signaling in Fibrotic Diseases. Cells 2022, 11, 2065. [Google Scholar] [CrossRef]
- Staley, B.K.; Irvine, K.D. Hippo Signaling in Drosophila: Recent Advances and Insights. Dev. Dyn. Off. Publ. Am. Assoc. Anat. 2012, 241, 3–15. [Google Scholar] [CrossRef]
- Liu, H.; Du, S.; Lei, T.; Wang, H.; He, X.; Tong, R.; Wang, Y. Multifaceted Regulation and Functions of YAP/TAZ in Tumors (Review). Oncol. Rep. 2018, 40, 16–28. [Google Scholar] [CrossRef]
- Ortega, Á.; Vera, I.; Diaz, M.; Navarro, C.; Rojas, M.; Torres, W.; Parra, H.; Salazar, J.; De Sanctis, J.; Bermúdez, V. The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises. Int. J. Mol. Sci. 2021, 23, 430. [Google Scholar] [CrossRef]
- Papavassiliou, K.A.; Sofianidi, A.A.; Papavassiliou, A.G. YAP/TAZ-TEAD Signalling Axis: A New Therapeutic Target in Malignant Pleural Mesothelioma. J. Cell. Mol. Med. 2024, 28, e18330. [Google Scholar] [CrossRef]
- Pocaterra, A.; Romani, P.; Dupont, S. YAP/TAZ Functions and Their Regulation at a Glance. J. Cell Sci. 2020, 133, jcs230425. [Google Scholar] [CrossRef]
- McDonald, C.B.; McIntosh, S.K.N.; Mikles, D.C.; Bhat, V.; Deegan, B.J.; Seldeen, K.L.; Saeed, A.M.; Buffa, L.; Sudol, M.; Nawaz, Z.; et al. Biophysical Analysis of Binding of WW Domains of the YAP2 Transcriptional Regulator to PPXY Motifs within WBP1 and WBP2 Adaptors. Biochemistry 2011, 50, 9616–9627. [Google Scholar] [CrossRef] [PubMed]
- Boopathy, G.T.K.; Hong, W. Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis. Front. Cell Dev. Biol. 2019, 7, 49. [Google Scholar] [CrossRef] [PubMed]
- Fu, M.; Hu, Y.; Lan, T.; Guan, K.-L.; Luo, T.; Luo, M. The Hippo Signalling Pathway and Its Implications in Human Health and Diseases. Signal Transduct. Target. Ther. 2022, 7, 376. [Google Scholar] [CrossRef] [PubMed]
- Luo, J.; Zou, H.; Guo, Y.; Tong, T.; Chen, Y.; Xiao, Y.; Pan, Y.; Li, P. The Oncogenic Roles and Clinical Implications of YAP/TAZ in Breast Cancer. Br. J. Cancer 2023, 128, 1611–1624. [Google Scholar] [CrossRef]
- Moon, H.; Park, H.; Chae, M.J.; Choi, H.J.; Kim, D.Y.; Ro, S.W. Activated TAZ Induces Liver Cancer in Collaboration with EGFR/HER2 Signaling Pathways. BMC Cancer 2022, 22, 423. [Google Scholar] [CrossRef]
- Hao, G.; Lv, T.; Wu, Y.; Wang, H.; Xing, W.; Wang, Y.; Li, C.; Zhang, Z.; Wang, Z.; Wang, W.; et al. The Hippo Signaling Pathway: A Potential Therapeutic Target Is Reversed by a Chinese Patent Drug in Rats with Diabetic Retinopathy. BMC Complement. Altern. Med. 2017, 17, 187. [Google Scholar] [CrossRef] [PubMed]
- Xie, J.; Wang, Y.; Ai, D.; Yao, L.; Jiang, H. The Role of the Hippo Pathway in Heart Disease. FEBS J. 2022, 289, 5819–5833. [Google Scholar] [CrossRef]
- Bertero, T.; Oldham, W.M.; Cottrill, K.A.; Pisano, S.; Vanderpool, R.R.; Yu, Q.; Zhao, J.; Tai, Y.; Tang, Y.; Zhang, Y.-Y.; et al. Vascular Stiffness Mechanoactivates YAP/TAZ-Dependent Glutaminolysis to Drive Pulmonary Hypertension. J. Clin. Investig. 2016, 126, 3313–3335. [Google Scholar] [CrossRef]
- Qian, X.; He, L.; Hao, M.; Li, Y.; Li, X.; Liu, Y.; Jiang, H.; Xu, L.; Li, C.; Wu, W.; et al. YAP Mediates the Interaction between the Hippo and PI3K/Akt Pathways in Mesangial Cell Proliferation in Diabetic Nephropathy. Acta Diabetol. 2021, 58, 47–62. [Google Scholar] [CrossRef]
- Gogia, N.; Chimata, A.V.; Deshpande, P.; Singh, A.; Singh, A. Hippo Signaling: Bridging the Gap between Cancer and Neurodegenerative Disorders. Neural Regen. Res. 2021, 16, 643–652. [Google Scholar] [CrossRef]
- Hong, L.; Li, X.; Zhou, D.; Geng, J.; Chen, L. Role of Hippo Signaling in Regulating Immunity. Cell. Mol. Immunol. 2018, 15, 1003–1009. [Google Scholar] [CrossRef] [PubMed]
- Fu, S.; Zhao, W.; Zhang, W.; Song, H.; Ji, H.; Tang, N. Hippo Signaling Pathway in Lung Development, Regeneration, and Diseases. Yi Chuan Hered. 2017, 39, 597–606. [Google Scholar] [CrossRef]
- Xie, H.; Wu, L.; Deng, Z.; Huo, Y.; Cheng, Y. Emerging Roles of YAP/TAZ in Lung Physiology and Diseases. Life Sci. 2018, 214, 176–183. [Google Scholar] [CrossRef] [PubMed]
- Byrne, A.J.; Maher, T.M.; Lloyd, C.M. Pulmonary Macrophages: A New Therapeutic Pathway in Fibrosing Lung Disease? Trends Mol. Med. 2016, 22, 303–316. [Google Scholar] [CrossRef] [PubMed]
- Liu, F.; Lagares, D.; Choi, K.M.; Stopfer, L.; Marinković, A.; Vrbanac, V.; Probst, C.K.; Hiemer, S.E.; Sisson, T.H.; Horowitz, J.C.; et al. Mechanosignaling through YAP and TAZ Drives Fibroblast Activation and Fibrosis. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2015, 308, L344–L357. [Google Scholar] [CrossRef] [PubMed]
- Piccolo, S.; Dupont, S.; Cordenonsi, M. The Biology of YAP/TAZ: Hippo Signaling and Beyond. Physiol. Rev. 2014, 94, 1287–1312. [Google Scholar] [CrossRef]
- Ghosh, A.K.; Vaughan, D.E. PAI-1 in Tissue Fibrosis. J. Cell. Physiol. 2012, 227, 493–507. [Google Scholar] [CrossRef]
- Samarakoon, R.; Higgins, S.P.; Higgins, C.E.; Higgins, P.J. TGF-Beta1-Induced Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells Requires Pp60(c-Src)/EGFR(Y845) and Rho/ROCK Signaling. J. Mol. Cell. Cardiol. 2008, 44, 527–538. [Google Scholar] [CrossRef]
- Link, P.A.; Choi, K.M.; Diaz Espinosa, A.M.; Jones, D.L.; Gao, A.Y.; Haak, A.J.; Tschumperlin, D.J. Combined Control of the Fibroblast Contractile Program by YAP and TAZ. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2022, 322, L23–L32. [Google Scholar] [CrossRef]
- Luo, J.; Yu, F.-X. GPCR-Hippo Signaling in Cancer. Cells 2019, 8, 426. [Google Scholar] [CrossRef]
- Zmajkovicova, K.; Bauer, Y.; Menyhart, K.; Schnoebelen, M.; Freti, D.; Boucher, M.; Renault, B.; Studer, R.; Birker-Robaczewska, M.; Klenk, A.; et al. GPCR-Induced YAP Activation Sensitizes Fibroblasts to Profibrotic Activity of TGFβ1. PLoS ONE 2020, 15, e0228195. [Google Scholar] [CrossRef] [PubMed]
- Milara, J.; Navarro, R.; Juan, G.; Peiró, T.; Serrano, A.; Ramón, M.; Morcillo, E.; Cortijo, J. Sphingosine-1-Phosphate Is Increased in Patients with Idiopathic Pulmonary Fibrosis and Mediates Epithelial to Mesenchymal Transition. Thorax 2012, 67, 147–156. [Google Scholar] [CrossRef] [PubMed]
- Huang, L.S.; Sudhadevi, T.; Fu, P.; Punathil-Kannan, P.-K.; Ebenezer, D.L.; Ramchandran, R.; Putherickal, V.; Cheresh, P.; Zhou, G.; Ha, A.W.; et al. Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts. Int. J. Mol. Sci. 2020, 21, 2064. [Google Scholar] [CrossRef] [PubMed]
- Huang, L.S.; Berdyshev, E.; Mathew, B.; Fu, P.; Gorshkova, I.A.; He, D.; Ma, W.; Noth, I.; Ma, S.-F.; Pendyala, S.; et al. Targeting Sphingosine Kinase 1 Attenuates Bleomycin-Induced Pulmonary Fibrosis. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2013, 27, 1749–1760. [Google Scholar] [CrossRef]
- Aravamudhan, A.; Haak, A.J.; Choi, K.M.; Meridew, J.A.; Caporarello, N.; Jones, D.L.; Tan, Q.; Ligresti, G.; Tschumperlin, D.J. TBK1 Regulates YAP/TAZ and Fibrogenic Fibroblast Activation. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2020, 318, L852–L863. [Google Scholar] [CrossRef]
- Helgason, E.; Phung, Q.T.; Dueber, E.C. Recent Insights into the Complexity of Tank-binding Kinase 1 Signaling Networks: The Emerging Role of Cellular Localization in the Activation and Substrate Specificity of TBK1. FEBS Lett. 2013, 587, 1230–1237. [Google Scholar] [CrossRef] [PubMed]
- Lin, K.C.; Moroishi, T.; Meng, Z.; Jeong, H.-S.; Plouffe, S.W.; Sekido, Y.; Han, J.; Park, H.W.; Guan, K.-L. Regulation of Hippo Pathway Transcription Factor TEAD by P38 MAPK-Induced Cytoplasmic Translocation. Nat. Cell Biol. 2017, 19, 996–1002. [Google Scholar] [CrossRef]
- Chen, Y.; Zhao, X.; Sun, J.; Su, W.; Zhang, L.; Li, Y.; Liu, Y.; Zhang, L.; Lu, Y.; Shan, H.; et al. YAP1/Twist Promotes Fibroblast Activation and Lung Fibrosis That Conferred by miR-15a Loss in IPF. Cell Death Differ. 2019, 26, 1832–1844. [Google Scholar] [CrossRef]
- Lee, K.-W.; Yeo, S.-Y.; Sung, C.O.; Kim, S.-H. Twist1 Is a Key Regulator of Cancer-Associated Fibroblasts. Cancer Res. 2015, 75, 73–85. [Google Scholar] [CrossRef]
- Tan, J.; Tedrow, J.R.; Nouraie, M.; Dutta, J.A.; Miller, D.T.; Li, X.; Yu, S.; Chu, Y.; Juan-Guardela, B.; Kaminski, N.; et al. Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12. J. Immunol. 2017, 198, 2269–2285. [Google Scholar] [CrossRef]
- Zhu, T.; Ma, Z.; Wang, H.; Jia, X.; Wu, Y.; Fu, L.; Li, Z.; Zhang, C.; Yu, G. YAP/TAZ Affects the Development of Pulmonary Fibrosis by Regulating Multiple Signaling Pathways. Mol. Cell. Biochem. 2020, 475, 137–149. [Google Scholar] [CrossRef] [PubMed]
- Gokey, J.J.; Sridharan, A.; Xu, Y.; Green, J.; Carraro, G.; Stripp, B.R.; Perl, A.-K.T.; Whitsett, J.A. Active Epithelial Hippo Signaling in Idiopathic Pulmonary Fibrosis. JCI Insight 2018, 3, e98738. [Google Scholar] [CrossRef] [PubMed]
- Antoniou, K.M.; Margaritopoulos, G.A.; Soufla, G.; Symvoulakis, E.; Vassalou, E.; Lymbouridou, R.; Samara, K.D.; Kappou, D.; Spandidos, D.A.; Siafakas, N.M. Expression Analysis of Akt and MAPK Signaling Pathways in Lung Tissue of Patients with Idiopathic Pulmonary Fibrosis (IPF). J. Recept. Signal Transduct. 2010, 30, 262–269. [Google Scholar] [CrossRef] [PubMed]
- Sun, Z.; Gong, X.; Zhu, H.; Wang, C.; Xu, X.; Cui, D.; Qian, W.; Han, X. Inhibition of Wnt/Β- C Atenin Signaling Promotes Engraftment of Mesenchymal Stem Cells to Repair Lung Injury. J. Cell. Physiol. 2014, 229, 213–224. [Google Scholar] [CrossRef]
- Akhmetshina, A.; Palumbo, K.; Dees, C.; Bergmann, C.; Venalis, P.; Zerr, P.; Horn, A.; Kireva, T.; Beyer, C.; Zwerina, J.; et al. Activation of Canonical Wnt Signalling Is Required for TGF-β-Mediated Fibrosis. Nat. Commun. 2012, 3, 735. [Google Scholar] [CrossRef]
- Liu, T.; Hu, B.; Choi, Y.Y.; Chung, M.; Ullenbruch, M.; Yu, H.; Lowe, J.B.; Phan, S.H. Notch1 Signaling in FIZZ1 Induction of Myofibroblast Differentiation. Am. J. Pathol. 2009, 174, 1745–1755. [Google Scholar] [CrossRef]
- Yan, P.; Liu, J.; Li, Z.; Wang, J.; Zhu, Z.; Wang, L.; Yu, G. Glycolysis Reprogramming in Idiopathic Pulmonary Fibrosis: Unveiling the Mystery of Lactate in the Lung. Int. J. Mol. Sci. 2023, 25, 315. [Google Scholar] [CrossRef]
- Chung, K.-P.; Hsu, C.-L.; Fan, L.-C.; Huang, Z.; Bhatia, D.; Chen, Y.-J.; Hisata, S.; Cho, S.J.; Nakahira, K.; Imamura, M.; et al. Mitofusins Regulate Lipid Metabolism to Mediate the Development of Lung Fibrosis. Nat. Commun. 2019, 10, 3390. [Google Scholar] [CrossRef]
- Koudelka, A.; Cechova, V.; Rojas, M.; Mitash, N.; Bondonese, A.; St. Croix, C.; Ross, M.A.; Freeman, B.A. Fatty Acid Nitroalkene Reversal of Established Lung Fibrosis. Redox Biol. 2022, 50, 102226. [Google Scholar] [CrossRef]
- Li, J.; Zhai, X.; Sun, X.; Cao, S.; Yuan, Q.; Wang, J. Metabolic Reprogramming of Pulmonary Fibrosis. Front. Pharmacol. 2022, 13, 1031890. [Google Scholar] [CrossRef]
- Umeda, Y.; Demura, Y.; Morikawa, M.; Anzai, M.; Kadowaki, M.; Ameshima, S.; Tsuchida, T.; Tsujikawa, T.; Kiyono, Y.; Okazawa, H.; et al. Prognostic Value of Dual-Time-Point 18F-FDG PET for Idiopathic Pulmonary Fibrosis. J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 2015, 56, 1869–1875. [Google Scholar] [CrossRef] [PubMed]
- Kashihara, T.; Mukai, R.; Oka, S.; Zhai, P.; Nakada, Y.; Yang, Z.; Mizushima, W.; Nakahara, T.; Warren, J.S.; Abdellatif, M.; et al. YAP Mediates Compensatory Cardiac Hypertrophy through Aerobic Glycolysis in Response to Pressure Overload. J. Clin. Investig. 2022, 132, e150595. [Google Scholar] [CrossRef] [PubMed]
- Koo, J.H.; Guan, K.-L. Interplay between YAP/TAZ and Metabolism. Cell Metab. 2018, 28, 196–206. [Google Scholar] [CrossRef] [PubMed]
- Yin, X.; Choudhury, M.; Kang, J.-H.; Schaefbauer, K.J.; Jung, M.-Y.; Andrianifahanana, M.; Hernandez, D.M.; Leof, E.B. Hexokinase 2 Couples Glycolysis with the Profibrotic Actions of TGF-β. Sci. Signal. 2019, 12, eaax4067. [Google Scholar] [CrossRef]
- Enzo, E.; Santinon, G.; Pocaterra, A.; Aragona, M.; Bresolin, S.; Forcato, M.; Grifoni, D.; Pession, A.; Zanconato, F.; Guzzo, G.; et al. Aerobic Glycolysis Tunes YAP/TAZ Transcriptional Activity. EMBO J. 2015, 34, 1349–1370. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, V.; Taine, E.G.; Meng, D.; Cui, T.; Tan, W. Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline. Int. J. Mol. Sci. 2024, 25, 3385. [Google Scholar] [CrossRef] [PubMed]
- Mohamadi, N.; Sharififar, F.; Pournamdari, M.; Ansari, M. A Review on Biosynthesis, Analytical Techniques, and Pharmacological Activities of Trigonelline as a Plant Alkaloid. J. Diet. Suppl. 2018, 15, 207–222. [Google Scholar] [CrossRef]
- Allred, K.F.; Yackley, K.M.; Vanamala, J.; Allred, C.D. Trigonelline Is a Novel Phytoestrogen in Coffee Beans. J. Nutr. 2009, 139, 1833–1838. [Google Scholar] [CrossRef]
- Ashihara, H.; Ludwig, I.A.; Katahira, R.; Yokota, T.; Fujimura, T.; Crozier, A. Trigonelline and Related Nicotinic Acid Metabolites: Occurrence, Biosynthesis, Taxonomic Considerations, and Their Roles in Planta and in Human Health. Phytochem. Rev. 2015, 14, 765–798. [Google Scholar] [CrossRef]
- Zeyada, M.S.; Eraky, S.M.; El-Shishtawy, M.M. Trigonelline Mitigates Bleomycin-Induced Pulmonary Inflammation and Fibrosis: Insight into NLRP3 Inflammasome and SPHK1/S1P/Hippo Signaling Modulation. Life Sci. 2024, 336, 122272. [Google Scholar] [CrossRef]
- Haak, A.J.; Kostallari, E.; Sicard, D.; Ligresti, G.; Choi, K.M.; Caporarello, N.; Jones, D.L.; Tan, Q.; Meridew, J.; Diaz Espinosa, A.M.; et al. Selective YAP/TAZ Inhibition in Fibroblasts via Dopamine Receptor D1 Agonism Reverses Fibrosis. Sci. Transl. Med. 2019, 11, eaau6296. [Google Scholar] [CrossRef] [PubMed]
- Moya, I.M.; Halder, G. Hippo–YAP/TAZ Signalling in Organ Regeneration and Regenerative Medicine. Nat. Rev. Mol. Cell Biol. 2019, 20, 211–226. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Kim, Y.H.; Kim, J.; Park, D.Y.; Bae, H.; Lee, D.-H.; Kim, K.H.; Hong, S.P.; Jang, S.P.; Kubota, Y.; et al. YAP/TAZ Regulates Sprouting Angiogenesis and Vascular Barrier Maturation. J. Clin. Investig. 2017, 127, 3441–3461. [Google Scholar] [CrossRef]
- Santos, D.M.; Pantano, L.; Pronzati, G.; Grasberger, P.; Probst, C.K.; Black, K.E.; Spinney, J.J.; Hariri, L.P.; Nichols, R.; Lin, Y.; et al. Screening for YAP Inhibitors Identifies Statins as Modulators of Fibrosis. Am. J. Respir. Cell Mol. Biol. 2020, 62, 479–492. [Google Scholar] [CrossRef]
- Zhao, X.; Sun, J.; Su, W.; Shan, H.; Zhang, B.; Wang, Y.; Shabanova, A.; Shan, H.; Liang, H. Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway. Int. J. Mol. Sci. 2018, 19, 1118. [Google Scholar] [CrossRef]
- Newman, D.J.; Cragg, G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770–803. [Google Scholar] [CrossRef]
- Li, C.; Li, Q.; Mei, Q.; Lu, T. Pharmacological Effects and Pharmacokinetic Properties of Icariin, the Major Bioactive Component in Herba Epimedii. Life Sci. 2015, 126, 57–68. [Google Scholar] [CrossRef]
- Huang, H.; Zhang, Z.; Qin, F.; Tang, W.; Liu, D.; Wu, P.; Jiao, F. Icariin Inhibits Chondrocyte Apoptosis and Angiogenesis by Regulating the TDP-43 Signaling Pathway. Mol. Genet. Genomic Med. 2019, 7, e00586. [Google Scholar] [CrossRef] [PubMed]
- Singh, W.R.; Devi, H.S.; Kumawat, S.; Sadam, A.; Appukuttan, A.V.; Patel, M.R.; Lingaraju, M.C.; Singh, T.U.; Kumar, D. Angiogenic and MMPs Modulatory Effects of Icariin Improved Cutaneous Wound Healing in Rats. Eur. J. Pharmacol. 2019, 858, 172466. [Google Scholar] [CrossRef]
- Li, Y.; Ding, X.; Li, H.; Zhang, C. Icariin Attenuates High Glucose-induced Type IV Collagen and Fibronectin Accumulation in Glomerular Mesangial Cells by Inhibiting Transforming Growth Factor-β Production and Signalling through G Protein-coupled Oestrogen Receptor 1. Clin. Exp. Pharmacol. Physiol. 2013, 40, 635–643. [Google Scholar] [CrossRef]
- Sun, X.; Cheng, H.; Liu, B.; Du, Y.; Dong, J.; Huang, J. Icariin Reduces LPS-Induced Acute Lung Injury in Mice Undergoing Bilateral Adrenalectomy by Regulating GRα. Eur. J. Pharmacol. 2020, 876, 173032. [Google Scholar] [CrossRef] [PubMed]
- Du, W.; Tang, Z.; Yang, F.; Liu, X.; Dong, J. Icariin Attenuates Bleomycin-Induced Pulmonary Fibrosis by Targeting Hippo/YAP Pathway. Biomed. Pharmacother. 2021, 143, 112152. [Google Scholar] [CrossRef] [PubMed]
- Zmajkovicova, K.; Menyhart, K.; Bauer, Y.; Studer, R.; Renault, B.; Schnoebelen, M.; Bolinger, M.; Nayler, O.; Gatfield, J. The Antifibrotic Activity of Prostacyclin Receptor Agonism Is Mediated through Inhibition of YAP/TAZ. Am. J. Respir. Cell Mol. Biol. 2019, 60, 578–591. [Google Scholar] [CrossRef]
- Paul, S.M.; Mytelka, D.S.; Dunwiddie, C.T.; Persinger, C.C.; Munos, B.H.; Lindborg, S.R.; Schacht, A.L. How to Improve R&D Productivity: The Pharmaceutical Industry’s Grand Challenge. Nat. Rev. Drug Discov. 2010, 9, 203–214. [Google Scholar] [CrossRef]
- Li, M.; Zhou, Y.; Wang, T.; Li, M.; Chen, X.; Zhang, T.; Wang, D.; Zhang, J. Nintedanib Exerts Anti-Pulmonary Fibrosis Activity via Inhibiting TANK-Binding Kinase 1 (TBK1) Phosphorylation. Chem. Commun. 2022, 58, 1199–1202. [Google Scholar] [CrossRef]
- Graham, K.; Lienau, P.; Bader, B.; Prechtl, S.; Naujoks, J.; Lesche, R.; Weiske, J.; Kuehnlenz, J.; Brzezinka, K.; Potze, L.; et al. Discovery of YAP1/TAZ Pathway Inhibitors through Phenotypic Screening with Potent Anti-Tumor Activity via Blockade of Rho-GTPase Signaling. Cell Chem. Biol. 2024, 31, 1247–1263.e16. [Google Scholar] [CrossRef] [PubMed]
- Huang, L.; Yang, X.; Feng, Y.; Huang, H.-X.; Hu, J.-Q.; Yan, P.-Y.; Pan, H.-D.; Xie, Y. ShaShen-MaiDong Decoction Attenuates Bleomycin-Induced Pulmonary Fibrosis by Inhibiting TGF-β/Smad3, AKT/MAPK, and YAP/TAZ Pathways. J. Ethnopharmacol. 2024, 118755. [Google Scholar] [CrossRef]
- Ohto-Fujita, E.; Shimizu, M.; Atomi, A.; Hiruta, H.; Hosoda, R.; Horinouchi, S.; Miyazaki, S.; Murakami, T.; Asano, Y.; Hasebe, Y.; et al. Eggshell Membrane and Its Major Component Lysozyme and Ovotransferrin Enhance the Secretion of Decorin as an Endogenous Antifibrotic Mediator from Lung Fibroblasts and Ameliorate Bleomycin-Induced Pulmonary Fibrosis. Biochem. Biophys. Rep. 2024, 39, 101806. [Google Scholar] [CrossRef]
Compound | Mechanism of Action | Experimental Study |
---|---|---|
Trigonelline | Attenuates lung SPHK1/S1P axis, decreases YAP/TAZ profibrotic phenotypes, and promotes matrix degradation | Mitigates BML-induced PF in rats [71] |
Dihydrexidine | DRD1 agonist elevates cAMP and promotes YAP/TAZ Ser127 phosphorylation | Reverses fibrosis in mice [72] |
Simvastatin | Modulates YAP/TAZ localization | Attenuates established lung fibrosis in BML-induced PF in mice [75] |
Melatonin | Promotes the translocation of YAP/TAZ into the nucleus | Mitigates BML-induced PF in mice, Attenuates TGF-β-induced fibrogenesis by activating the YAP/TAZ pathway [76] |
Icariin | Blocks YAP function | Prevents BML-induced PF in rats [83] |
ACT-333679 (Selexipag) | YAP/TAZ inhibition through prostacyclin receptor activation | Inhibits the TGF-β1-induced transformation of fibroblasts into myofibroblasts [84] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Papavassiliou, K.A.; Sofianidi, A.A.; Spiliopoulos, F.G.; Gogou, V.A.; Gargalionis, A.N.; Papavassiliou, A.G. YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis. Cells 2024, 13, 1519. https://doi.org/10.3390/cells13181519
Papavassiliou KA, Sofianidi AA, Spiliopoulos FG, Gogou VA, Gargalionis AN, Papavassiliou AG. YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis. Cells. 2024; 13(18):1519. https://doi.org/10.3390/cells13181519
Chicago/Turabian StylePapavassiliou, Kostas A., Amalia A. Sofianidi, Fotios G. Spiliopoulos, Vassiliki A. Gogou, Antonios N. Gargalionis, and Athanasios G. Papavassiliou. 2024. "YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis" Cells 13, no. 18: 1519. https://doi.org/10.3390/cells13181519