JNJ0966 inhibits PDGF-BB-induced airway smooth muscle cell proliferation and extracellular matrix production by regulating MMP-9
Main Article Content
Keywords
ASMCs, asthma, JNJ0966, MMP-9, PDGF-BB
Abstract
The increased proliferation and extracellular matrix (ECM) production of airway smooth muscle cells (ASMCs) are crucial factors in asthma progression. JNJ0966, one of the metalloproteinase-9 (MMP-9)-specific inhibitors, has been demonstrated to be involved in the progression and development of diversified diseases. Nevertheless, the function of JNJ0966 in ASMCs remains unclear. This study aimed at investigating the effects of JNJ0966 on asthma progression. In our study, the platelet-derived growth factor BB (PDGF-BB) was first utilized to stimulate the cell model for asthma. Results demonstrated that the cell viability of ASMCs was increased by PDGF-BB (0, 10, 20, and 30 ng/mL) in a dose-dependent manner. Further investigation revealed that JNJ0966 inhibited the cell activity and migration ability of PDGF-BB-induced ASMCs. In addition, JNJ0966 relieved ECM deposition in PDGF-BB-induced ASMCs. Finally, through rescue assays, the results showed that overexpression of MMP-9 reversed the inhibitory effects of JNJ0966 on cell viability and ECM deposition in ASMCs. In conclusion, our findings suggested that JNJ0966 inhibited PDGF-BB-induced ASMC proliferation and ECM production by modulating MMP-9. These findings might provide novel insight for the treatment of asthma.
References
2. Mims JW. Asthma: definitions and pathophysiology. Int Forum Allergy Rhinol. 2015;5 (Suppl 1):S2–6. 10.1002/alr.21609
3. Huang K, Yang T, Xu J, Yang L, Zhao J, Zhang X, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet. 2019;394(10196):407–18. 10.1016/S0140-6736(19)31147-X
4. Padem N, Saltoun C. Classification of asthma. Allergy Asthma Proc. 2019;40(6):385–8. 10.2500/aap.2019.40.4253
5. Turcotte SE, Lougheed MD. Cough in asthma. Curr Opin Pharmacol. 2011;11(3):231–7. 10.1016/j.coph.2011.04.008
6. Makinde T, Murphy RF, Agrawal DK. The regulatory role of TGF-beta in airway remodeling in asthma. Immunol Cell Biol. 2007;85(5):348–56. 10.1038/sj.icb.7100044
7. Zhao C, Wu AY, Yu X, Gu Y, Lu Y, Song X, et al. Microdomain elements of airway smooth muscle in calcium regulation and cell proliferation. J Physiol Pharmacol. 2018;69(2):151–63. 10.26402/jpp.2018.2.01
8. Zhang S, Shao Q, Jia L, Zhou F. ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells. Signa Vitae. 2021;17(3):206–13. 10.22514/sv.2021.078
9. Boulet LP. Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Curr Opin Pulm Med. 2018;24(1):56–62. 10.1097/MCP.0000000000000441
10. Banno A, Reddy AT, Lakshmi SP, Reddy RC. Bidirectional interaction of airway epithelial remodeling and inflammation in asthma. Clin Sci. 2020;134(9):1063–79. 10.1042/CS20191309
11. Bai TR, Cooper J, Koelmeyer T, Paré PD, Weir TD. The effect of age and duration of disease on airway structure in fatal asthma. Am J Respir Crit Care Med. 2000;162(2 Pt 1):663–9. 10.1164/ajrccm.162.2.9907151
12. Johnson PR, Burgess JK, Underwood PA, Au W, Poniris MH, Tamm M, et al. Extracellular matrix proteins modulate asthmatic airway smooth muscle cell proliferation via an autocrine mechanism. J Allergy Clini Immunol. 2004;113(4):690–6. 10.1016/j.jaci.2003.12.312
13. Eapen MS, Kota A, Vindin H, McAlinden KD, Xenaki D, Oliver BG, et al. Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease. Clin Sci. 2018;132(14):1615–27. 10.1042/CS20180398
14. Liu Y, Sun X, Wu Y, Fang P, Shi H, Xu J, et al. Effects of miRNA-145 on airway smooth muscle cells function. Mol Cell Biochem. 2015;409(1–2):135–43. 10.1007/s11010-015-2519-7
15. Li P, Liu Y, Yi B, Wang G, You X, Zhao X, et al. microRNA-638 is highly expressed in human vascular smooth muscle cells and inhibits PDGF-BB-induced cell proliferation and migration through targeting orphan nuclear receptor NOR1. Cardiovasc Res. 2013;99(1):185–93. 10.1093/cvr/cvt082
16. Hu P, Guan K, Feng Y, Ma C, Song H, Li Y, et al. miR-638 inhibits immature sertoli cell growth by indirectly inactivating PI3K/AKT pathway via SPAG1 gene. Cell Cycle. 2017;16(23):2290–300. 10.1080/15384101.2017.1380130
17. Parameswaran K, Willems-Widyastuti A, Alagappan VK, Radford K, Kranenburg AR, Sharma HS. Role of extracellular matrix and its regulators in human airway smooth muscle biology. Cell Biochem Biophys. 2006;44(1):139–46. 10.1385/CBB:44:1:139
18. Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 Biosensors: recent advances. Sensors. 2018;18(10):3249. 10.3390/s18103249
19. Cho SH, Ryu CH, Oh CK. Plasminogen activator inhibitor-1 in the pathogenesis of asthma. Exp Biol Med. 2004;229(2):138–46. 10.1177/153537020422900202
20. Zou F, Zhang J, Xiang G, Jiao H, Gao H. Association of matrix metalloproteinase 9 (MMP-9) polymorphisms with asthma risk: a meta-analysis. Can Respir J. 2019;2019:9260495. 10.1155/2019/9260495
21. Scannevin RH, Alexander R, Haarlander TM, Burke SL, Singer M, Huo C, et al. Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation. J Biol Chem. 2017;292(43):17963–74. 10.1074/jbc.M117.806075
22. Boon L, Ugarte-Berzal E, Martens E, Fiten P, Vandooren J, Janssens R, et al. Citrullination as a novel posttranslational modification of matrix metalloproteinases. Matrix Biol. 2021;95:68–83. 10.1016/j.matbio.2020.10.005
23. Liu L, Ye Y, Zhu X. MMP-9 secreted by tumor associated macrophages promoted gastric cancer metastasis through a PI3K/AKT/Snail pathway. Biomed Pharmacother. 2019;117:109096. 10.1016/j.biopha.2019.109096
24. Liu Y, Wei L, He C, Chen R, Meng L. Lipoxin A4 inhibits ovalbumin-induced airway inflammation and airway remodeling in a mouse model of asthma. Chem Biol Interact. 2021;349:109660. 10.1016/j.cbi.2021.109660
25. Fehrenbach H, Wagner C, Wegmann M. Airway remodeling in asthma: what really matters. Cell Tissue Res. 2017;367(3):551–69. 10.1007/s00441-016-2566-8
26. Paré PD, Roberts CR, Bai TR, Wiggs BJ. The functional consequences of airway remodeling in asthma. Monaldi Arch Chest Dis. 1997;52(6):589–96. 10.1155/2010/318029
27. Sun Q, Liu L, Mandal J, Molino A, Stolz D, Tamm M, et al. PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts. Cell Signal. 2016;28(4):307–15. 10.1016/j.cellsig.2016.01.004
28. Dai Y, Li Y, Cheng R, Gao J, Li Y, Lou C. TRIM37 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells. Biomed Pharmacother. 2018;101:24–9. 10.1016/j.biopha.2018.02.057
29. Yang W, Chen Y, Huang C, Wang W, Huang C, Li Y. miR-18a inhibits PI3K/AKT signaling pathway to regulate PDGF BB-induced airway smooth muscle cell proliferation and phenotypic transformation. Physiol Res. 2021;70(6):883–92. 10.33549//physiolres.934753
30. Wang Z, Li R, Zhong R. Extracellular matrix promotes proliferation, migration and adhesion of airway smooth muscle cells in a rat model of chronic obstructive pulmonary disease via upregulation of the PI3K/AKT signaling pathway. Mol Med Rep. 2018;18(3):3143–52. 10.3892/mmr.2018.9320
31. Akbari Dilmaghnai N, Shoorei H, Sharifi G, Mohaqiq M, Majidpoor J, Dinger ME, et al. Non-coding RNAs modulate function of extracellular matrix proteins. Biomed Pharmacother. 2021;136:111240. 10.1016/j.biopha.2021.111240
32. Yang Z, Qu Z, Yi M, Lv Z, Wang Y, Shan Y, et al. MiR-204-5p Inhibits transforming growth factor-β1-induced proliferation and extracellular matrix production of airway smooth muscle cells by regulating Six1 in asthma. Int Arch Allergy Immunol. 2020;181(4):239–48. 10.1159/000505064
33. Cheng W, Yan K, Xie LY, Chen F, Yu HC, Huang YX, et al. MiR-143-3p controls TGF-β1-induced cell proliferation and extracellular matrix production in airway smooth muscle via negative regulation of the nuclear factor of activated T cells 1. Mol Immunol. 2016;78:133-9. 10.1016/j.molimm.2016.09.004
34. Fang P, Deng WJ, Fan N, Shi J, Shi HY, Ou L, et al. AMOTL2 restrains transforming growth factor-β1-induced proliferation and extracellular matrix deposition of airway smooth muscle cells via the down-regulation of YAP1 activation. Environ Toxicol. 2021;36(11):2225–35. 10.1002/tox.23336
35. Januskevicius A, Vaitkiene S, Gosens R, Janulaityte I, Hoppenot D, Sakalauskas R, et al. Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma. BMC Pulm Med. 2016;16(1):94. 10.1186/s12890-016-0254-9
36. Zhang Q, Ni Y, Wang S, Agbana YL, Han Q, Liu W, et al. G6PD upregulates Cyclin E1 and MMP9 to promote clear cell renal cell carcinoma progression. Int J Med Sci. 2022;19(1):47-64. 10.7150/ijms.58902
37. Luo S, Li W, Wu W, Shi Q. Elevated expression of MMP8 and MMP9 contributes to diabetic osteoarthritis progression in a rat model. J Orthop Surg Res. 2021;16(1):64. 10.1186/s13018-021-02208-9
38. Xu Z, Zuo Z, Dong D, Liu J, Tang Y, Gu Y, et al. Downregulated lncRNA UCA1 accelerates proliferation and migration of vascular smooth muscle cells by epigenetic regulation of MMP9. Exp Ther Med. 2020;19(6):3589–94. 10.3892/etm.2020.8639
39. Yu F, Sun Y, Yu J, Ding Z, Wang J, Zhang L, et al. ORMDL3 is associated with airway remodeling in asthma via the ERK/MMP-9 pathway. Mol Med Rep. 2017;15(5):2969–76. 10.3892/mmr.2017.6413
40. Barbaro MP, Spanevello A, Palladino GP, Salerno FG, Lacedonia D, Carpagnano GE. Exhaled matrix metalloproteinase--9 (MMP-9) in different biological phenotypes of asthma. Eur J Intern Med. 2014;25(1):92–6. 10.1016/j.ejim.2013.08.705