Immune response regulation by transduced mesenchymal stem cells with decorin gene on bleomycin-induced lung injury, fibrosis, and inflammation
Main Article Content
Keywords
cell therapy, fibrosis, gene therapy, lung, Immune response, Allergy
Abstract
Background: Pulmonary fibrosis is a pathological hallmark of lung injury. It is an aggressive disease that replaces normal lung parenchyma by fibrotic tissue. The transforming growth factor-beta–mothers against decapentaplegic homolog 3 (TGF-β1–Smad3) signaling pathway plays a key role in regulating lung fibrosis. Decorin (DCN), a small leucine-rich proteoglycan, has a modulatory effect on the immune system by reversibly binding with TGF-β and reducing its bioavailability. Mesenchymal stem cell (MSC) therapy is a new strategy that has an immune-modulatory capacity.
Objective: The aim of this study was to introduce a new therapeutic approach to harness remodeling in injured lung.
Material and Methods: Bone marrow MSCs were isolated and transduced by decorin gene. Lung injury was induced by bleomycin and mice were treated with MSCs, MSCs–decorin, and decorin. Then, oxidative stress biomarkers, remodeling biomarkers, bronchoalveolar lavage cells, and histopathology study were conducted.
Results: Reduced catalase and superoxide dismutase increased due to treatments. Elevated malondialdehyde, hydroxyproline, TGF-β levels, and polymorphonuclear cells count decreased in the treated groups. Additionally, the histopathology of lung tissues showed controlled inflammation and fibrosis.
Conclusion: Transfected decorin gene to MSCs and used cell therapy could control remodeling and bleomycin-induced lung injury.
References
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25. Mohan RR, Gupta R, Mehan MK, Cowden JW, Sinha S. Decorin transfection suppresses profibrogenic genes and myofibroblast formation in human corneal fibroblasts. Exper Eye Res. 2010;91:238–45. 10.1016/j.exer.2010.05.013
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27. Chen S, Young MF, Chakravarti S, Birk DE. Interclass small leucine-rich repeat proteoglycan interactions regulate collagen fibrillogenesis and corneal stromal assembly. Matrix Biol. 2014;35:103–11. 10.1016/j.matbio.2014.01.004
28. Robinson PS, Huang TF, Kazam E, Iozzo RV, Birk DE, Soslowsky LJ. Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice. J Biomech Eng. 2005;127:181–5. 10.1115/1.1835363
29. Yin J, Yan F, Zheng R, Wu R, Athari SS. Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma. Allergol Immunopathol (Madr). 2023;51(1):110–5. 10.15586/aei.v51i1.746
30. Lin WY, Oh SKW, Choo ABH, George AJT. Activated T cells modulate immunosuppression by embryonic-and bone-marrow-derived mesenchymal stromal cells through a feedback mechanism. Cytotherapy. 2012;14:274–84. 10.3109/14653249.2011.635853
31. Wang D, Nasab EM, Athari SS. Study effect of Baicalein encapsulated/loaded chitosan-nanoparticle on allergic asthma pathology in mouse model. Saudi J Biol Sci. 2021;28:4311–7. 10.1016/j.sjbs.2021.04.009
32. Lin Y-D, Fan X-L, Zhang H, Fang S-B, Li C-L, Deng M-X, et al. The genes involved in asthma with the treatment of human embryonic stem cell-derived mesenchymal stem cells. Mol Immunol. 2018;95:47–55. 10.1016/j.molimm.2018.01.013
33. Jiling R, Yongzhe L, Ye Y, Lifeng F, Xiaotong Z, Zongjin L, et al. Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice. Int Immunopharmacol. 2021;91:107288. 10.1016/j.intimp.2020.107288
2. Song X, Liu W, Xie S, Wang M, Cao G, Mao C, et al. All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-b1/Smad3 signaling pathway in rats. Lab Investigat. 2013;93:1219–31. 10.1038/labinvest.2013.108
3. Grande NR, Peão MND, de Sá CM, Águas AP. Lung fibrosis induced by bleomycin: structural changes and overview of recent advances. Scan Microscopy. 1998;12(3):487–94.
4. Mori H, Tanaka H, Kawada K, Nagai H, Koda A. Suppressive effects of tranilast on pulmonary fibrosis and activation of alveolar macrophages in mice treated with bleomycin: role of alveolar macrophages in the fibrosis. Jpn J Pharmacol. 1995;67:279–89. 10.1254/jjp.67.279
5. Khalil N, O’Connor RN, Flanders KC, Shing W, Whitman CI. Regulation of type II alveolar epithelial cell proliferation by TGF-beta during bleomycin induced lung injury in rats. Am J Physiol. 1994;267:498–507. 10.1152/ajplung.1994.267.5.L498
6. Madtes DK, Busby HK, Strandjord TP, Clark JG. Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycin-induced lung injury in rats. Am J Resp Cell Mol Biol. 1994;11:540–51. 10.1165/ajrcmb.11.5.7524566
7. Santana A, Saxena B, Noble NA, Gold LI, Marshall BC. Increased expression of transforming growth factor beta isoforms in bleomycin induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 1995;13:34–44. 10.1165/ajrcmb.13.1.7541221
8. Zhang K, Flanders KC, Phan SH. Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis. Am J Pathol 1995;147:352–61.
9. Zhang R, Yin Z, Pan J, Zhai C, Athari SS, Dong L. Effect of transfected induced pluripotent stem cells with decorin gene on control of lung remodeling in allergic asthma. J Invest Med. 2023;71(3):235–43. 10.1177/10815589221140590
10. Bao X-h, Gao F, Athari SS, Wang H. Immunomodulatory effect of IL-35 gene-transfected mesenchymal stem cells on allergic asthma. Fundam Clin Pharmacol. 2023;37(1):116–24. 10.1111/fcp.12823
11. Huang M, Nasab EM, Athari SS. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J Biol Sci. 2021;28:6957–62. 10.1016/j.sjbs.2021.07.071
12. Hou C, Sun F, Liang Y, Nasab EM, Athari SS. Effect of transduced mesenchymal stem cells with IL-10 gene on control of allergic asthma. AllergolImmunopathol (Madr). 2023;51(2):45–51. 10.15586/aei.v51i2.789
13. Hajimohammadi B, Athari SM, Abdollahi M, Vahedi G, Athari SS. Oral administration of acrylamide worsens the inflammatory responses in the airways of asthmatic mice through agitation of oxidative stress in the lungs. Front Immunol. 2020;11:1940. 10.3389/fimmu.2020.01940
14. Reinert T, da Rocha Baldotto CS, Nunes FAP, de Souza Scheliga AA. Bleomycin-induced lung injury. J Cancer Res. 2013;Art ID:480608. 10.1155/2013/480608
15. Shimbori C, Shiota N, Okunishi H. Effects of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on the pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Eur J Pharmacol. 2011;650(1):424–30. 10.1016/j.ejphar.2010.09.084
16. Marshall RP, McAnulty RJ, Laurent GJ. The pathogenesis of pulmonary fibrosis: is there a fibrosis gene? Int J Biochem Cell Biol. 1997;29:107–20. 10.1016/S1357-2725(96)00141-0
17. Giri SN, Hyde DM, Hollinger MA. Effect of antibody to transforming growth factor-B on bleomycin-induced accumulation of lung collagen in mice. Thorax. 1993;48:959–66. 10.1136/thx.48.10.959
18. Wang Q, Wang Y, Hyde DM, Gotwals PJ, Koteliansky VE, Ryan ST, et al. Reduction of bleomycin induced lung fibrosis transforming growth factor-B soluble receptor in hamsters. Thorax. 1999;54:805–12. 10.1136/thx.54.9.805
19. Pittet J-F, Griffiths MJD, Geiser T, Kaminski N, Dalton SL, Huang X, et al. TGF-b is a critical mediator of acute lung injury. J Clin Invest. 2001;107:1537–44. 10.1172/JCI11963
20. Specks U, Nerlich A, Colby TV, Wiest I, Timpl R. Increased expression of type VI collagen in lung fibrosis. Am J Respir Crit Care Med. 1995;151:1956–64. 10.1164/ajrccm.151.6.7767545
21. Marchica CL, Pinelli V, Borges M, Zummer J, Narayanan V, Iozzo RV, et al. A role for decorin in a murine model of allergen-induced asthma. Am J Physiol Lung Cell Mol Physiol. 2011;300:863–73. 10.1152/ajplung.00300.2009
22. Salerno FG, Pinelli V, Pini L, Tuma B, Iozzo RV, Ludwig MS. Effect of PEEP on induced constriction is enhanced in decorin-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2007;293:1111–7. 10.1152/ajplung.00095.2007
23. Markmann A, Hausser H, Schönherr E, Kresse H. Influence of decorin expression on transforming growth factor-B mediated collagen gel retraction and biglycan induction. Matrix Biol. 2000;19:631–6. 10.1016/S0945-053X(00)00097-4
24. Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H. Decorin core protein fragment Leu 155-Val 260 interacts with TGF-b but does not compete for decorin binding to type I collagen. Arch Biochem Biophys. 1998;355:241–8. 10.1006/abbi.1998.0720
25. Mohan RR, Gupta R, Mehan MK, Cowden JW, Sinha S. Decorin transfection suppresses profibrogenic genes and myofibroblast formation in human corneal fibroblasts. Exper Eye Res. 2010;91:238–45. 10.1016/j.exer.2010.05.013
26. Allawadhi P, Singh V, Khurana I, Rawat PS, Renushe AP, Khurana A, et al. Decorin as a possible strategy for the amelioration of COVID-19. Med Hypotheses. 2021;152:110612. 10.1016/j.mehy.2021.110612
27. Chen S, Young MF, Chakravarti S, Birk DE. Interclass small leucine-rich repeat proteoglycan interactions regulate collagen fibrillogenesis and corneal stromal assembly. Matrix Biol. 2014;35:103–11. 10.1016/j.matbio.2014.01.004
28. Robinson PS, Huang TF, Kazam E, Iozzo RV, Birk DE, Soslowsky LJ. Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice. J Biomech Eng. 2005;127:181–5. 10.1115/1.1835363
29. Yin J, Yan F, Zheng R, Wu R, Athari SS. Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma. Allergol Immunopathol (Madr). 2023;51(1):110–5. 10.15586/aei.v51i1.746
30. Lin WY, Oh SKW, Choo ABH, George AJT. Activated T cells modulate immunosuppression by embryonic-and bone-marrow-derived mesenchymal stromal cells through a feedback mechanism. Cytotherapy. 2012;14:274–84. 10.3109/14653249.2011.635853
31. Wang D, Nasab EM, Athari SS. Study effect of Baicalein encapsulated/loaded chitosan-nanoparticle on allergic asthma pathology in mouse model. Saudi J Biol Sci. 2021;28:4311–7. 10.1016/j.sjbs.2021.04.009
32. Lin Y-D, Fan X-L, Zhang H, Fang S-B, Li C-L, Deng M-X, et al. The genes involved in asthma with the treatment of human embryonic stem cell-derived mesenchymal stem cells. Mol Immunol. 2018;95:47–55. 10.1016/j.molimm.2018.01.013
33. Jiling R, Yongzhe L, Ye Y, Lifeng F, Xiaotong Z, Zongjin L, et al. Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice. Int Immunopharmacol. 2021;91:107288. 10.1016/j.intimp.2020.107288
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Jul 1, 2024
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Xu, W., Kun Li, C., Yang, L. S., Mehrabi Nasab, E., Shamsadin Athari, S., & Dong Gu, W. (2024). Immune response regulation by transduced mesenchymal stem cells with decorin gene on bleomycin-induced lung injury, fibrosis, and inflammation. Allergologia Et Immunopathologia, 52(4), 53-59. https://doi.org/10.15586/aei.v52i4.1104
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How to Cite
Xu, W., Kun Li, C., Yang, L. S., Mehrabi Nasab, E., Shamsadin Athari, S., & Dong Gu, W. (2024). Immune response regulation by transduced mesenchymal stem cells with decorin gene on bleomycin-induced lung injury, fibrosis, and inflammation. Allergologia Et Immunopathologia, 52(4), 53-59. https://doi.org/10.15586/aei.v52i4.1104