Induced Pluripotent Stem-cells Inhibit Experimental Bleomycin-induced Pulmonary Fibrosis through Regulation of the Insulin-like Growth Factor Signaling
Regulation of the IGF Signaling by IPSCs
-
Paria Bayati
,
Marjan Taherian
,
Mohammad-Ali Assarehzadegan
,
Mansoureh Soleimani
,
Hadi Poormoghim
,
Nazanin Mojtabavi
Abstract
Idiopathic pulmonary fibrosis (IPF) is among the illnesses with a high mortality rate, yet no specific cause has been identified; as a result, successful treatment has not been achieved. Among the novel approaches for treating such hard-to-cure diseases are induced pluripotent stem cells (IPSCs). Some studies have shown these cells’ potential in treating IPF. Therefore, we aimed to investigate the impact of IPSCs on insulin-like growth factor (Igf) signaling as a major contributor to IPF pathogenesis.
C57BL/6 mice were intratracheally instilled with Bleomycin (BLM) or phosphate-buffered saline; the next day, half of the bleomycin group received IPSCs through tail vein injection. Hydroxyproline assay and histologic examinations have been performed to assess lung fibrosis. The gene expression was evaluated using specific primers for Igf-1, Igf-2, and insulin receptor substrate 1 (Irs-1) genes and SYBR green qPCR master mix. The data have been analyzed using the 2-ΔΔCT method.
The mice that received Bleomycin showed histological characteristics of the fibrotic lung injury, which was significantly ameliorated after treatment with IPSCs comparable to the control group. Furthermore, gene expression analyses revealed that in the BLM group, Igf1, Igf2, and Irs1 genes were significantly upregulated, which were returned to near-normal levels after treatment with IPSCs.
IPSCs could modulate the bleomycin-induced upregulation of Igf1, Igf2, and Irs1 genes. This finding reveals a new aspect of the therapeutic impact of the IPSCs on IPF, which could be translated into other fibrotic disorders.
1. Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J Clin Med. 2018;7(8):201.
2. Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012;21(126):355-61.
3. Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, et al. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res. 2021;22(1):197.
4. Valenzuela C, Torrisi SE, Kahn N, Quaresma M, Stowasser S, Kreuter M. Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme. Respir Res. 2020;21(1):7.
5. Wuyts WA, Wijsenbeek M, Bondue B, Bouros D, Bresser P, Robalo Cordeiro C, et al. Idiopathic Pulmonary Fibrosis: Best Practice in Monitoring and Managing a Relentless Fibrotic Disease. Respiration. 2020;99(1):73-82.
6. Fujimoto H, Kobayashi T, Azuma A. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis. Clin Med Insights Circ Respir Pulm Med. 2015;9(Suppl 1):179-85.
7. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32.
8. Kaunisto J, Salomaa ER, Hodgson U, Kaarteenaho R, Kankaanranta H, Koli K, et al. Demographics and survival of patients with idiopathic pulmonary fibrosis in the FinnishIPF registry. ERJ Open Res. 2019;5(3):00170-2018.
9. Gazdhar A, Grad I, Tamo L, Gugger M, Feki A, Geiser T. The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor. Stem Cell Res Ther. 2014;5(6):123.
10. How CK, Chien Y, Yang KY, Shih HC, Juan CC, Yang YP, et al. Induced pluripotent stem cells mediate the release of interferon gamma-induced protein 10 and alleviate bleomycin-induced lung inflammation and fibrosis. Shock. 2013;39(3):261-70.
11. Zhou Y, Gao Y, Zhang W, Chen Y, Jin M, Yang Z. Exosomes derived from induced pluripotent stem cells suppresses M2-type macrophages during pulmonary fibrosis via miR-302a-3p/TET1 axis. Int Immunopharmacol. 2021;99:108075.
12. Zhou Y, He Z, Gao Y, Zheng R, Zhang X, Zhao L, et al. Induced Pluripotent Stem Cells Inhibit Bleomycin-Induced Pulmonary Fibrosis in Mice through Suppressing TGF-beta1/Smad-Mediated Epithelial to Mesenchymal Transition. Front Pharmacol. 2016;7(1):430.
13. Zhou Y, Zhang Q, Gao Y, Tan M, Zheng R, Zhao L, et al. Induced pluripotent stem cell-conditioned medium suppresses pulmonary fibroblast-to-myofibroblast differentiation via the inhibition of TGF-beta1/Smad pathway. Int J Mol Med. 2018;41(1):473-84.
14. Heukels P, Moor CC, von der Thusen JH, Wijsenbeek MS, Kool M. Inflammation and immunity in IPF pathogenesis and treatment. Respir Med. 2019;147:79-91.
15. Garrett SM, Hsu E, Thomas JM, Pilewski JM, Feghali-Bostwick C. Insulin-like growth factor (IGF)-II- mediated fibrosis in pathogenic lung conditions. PLoS One. 2019;14(11):e0225422.
16. Guiot J, Henket M, Corhay JL, Moermans C, Louis R. Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7. PLoS One. 2017;12(2):e0171344.
17. Hernandez DM, Kang JH, Choudhury M, Andrianifahanana M, Yin X, Limper AH, et al. IPF pathogenesis is dependent upon TGFbeta induction of IGF-1. FASEB J. 2020;34(4):5363-88.
18. Hosono T, Bando M, Mizushina Y, Sata M, Hagiwara K, Sugiyama Y. Inhibitory effects of somatostatin analogue in bleomycin-induced pulmonary fibrosis. Exp Lung Res. 2021;47(6):280-8.
19. Renaud L, da Silveira WA, Takamura N, Hardiman G, Feghali-Bostwick C. Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis. Front Immunol. 2020;11(3):383.
20. Sun W, Jing X, Yang X, Huang H, Luo Q, Xia S, et al. Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation. Aging (Albany N Y). 2021;13(14):18852-69.
21. Xiao H, Huang X, Wang S, Liu Z, Dong R, Song D, et al. Metformin ameliorates bleomycin-induced pulmonary fibrosis in mice by suppressing IGF-1. Am J Transl Res. 2020;12(3):940-9.
22. Kim BN, Ahn DH, Kang N, Yeo CD, Kim YK, Lee KY, et al. TGF-beta induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci Rep. 2020;10(1):10597.
23. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156-72.
24. Bitterman P. Fibroblast-Matrix Cross-Talk in Idiopathic Pulmonary Fibrosis: Cross-Links at the Crossroads. Am J Respir Cell Mol Biol. 2018;58(5):547-8.
25. Ribatti D, Tamma R, Annese T. Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Transl Oncol. 2020;13(6):100773.
26. Liu X, Yun F, Shi L, Li ZH, Luo NR, Jia YF. Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer. Asian Pac J Cancer Prev. 2015;16(15):6201-6.
27. Zhu QQ, Ma C, Wang Q, Song Y, Lv T. The role of TWIST1 in epithelial-mesenchymal transition and cancers. Tumour Biol. 2016;37(1):185-97.
28. Ning X, Zhang K, Wu Q, Liu M, Sun S. Emerging role of Twist1 in fibrotic diseases. J Cell Mol Med. 2018;22(3):1383-91.
29. Ruan W, Ying K. Abnormal expression of IGF-binding proteins, an initiating event in idiopathic pulmonary fibrosis? Pathol Res Pract. 2010;206(8):537-43.
30. Hakuno F, Takahashi SI. IGF1 receptor signaling pathways. J Mol Endocrinol. 2018;61(1):T69-T86.
31. Shaw LM. Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-dependent activation of phosphoinositide 3-OH kinase and promotion of invasion. Mol Cell Biol. 2001;21(15):5082-93.
32. Hua H, Kong Q, Yin J, Zhang J, Jiang Y. Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy. J Hematol Oncol. 2020;13(1):64.
33. Wilker E, Lu J, Rho O, Carbajal S, Beltran L, DiGiovanni J. Role of PI3K/Akt signaling in insulin-like growth factor-1 (IGF-1) skin tumor promotion. Mol Carcinog. 2005;44(2):137-45.
34. Ma X, Bai Y. IGF-1 activates the P13K/AKT signaling pathway via upregulation of secretory clusterin. Mol Med Rep. 2012;6(6):1433-7.
35. Matsunami T, Sato Y, Ariga S, Sato T, Shimomura T, Kashimura H, et al. Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism. 2011;60(6):805-14.
36. Peng CH, Yang YS, Chan KC, Wang CJ, Chen ML, Huang CN. Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase. J Agric Food Chem. 2014;62(40):9736-43.
37. Zhao Q, Zhang CL, Xiang RL, Wu LL, Li L. CTRP15 derived from cardiac myocytes attenuates TGFbeta1-induced fibrotic response in cardiac fibroblasts. Cardiovasc Drugs Ther. 2020;34(5):591-604.
38. Carey BW, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, et al. Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci U S A. 2009;106(1):157-62.
39. Ren Y, Deng CL, Wan WD, Zheng JH, Mao GY, Yang SL. Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation. Mol Med Rep. 2015;11(4):2471-6.
40. Izadi E, Vafashoar F, Jorbozedar P, Safari P, Assarehzadegan MA, Poormoghim H, et al. Effect of Progesterone on Expression of MMP7 and MMP13 in Lungs of Female Mice. Iran J Allergy Asthma Immunol. 2018;17(5):485-9.
41. Zhong H, Fan XL, Fang SB, Lin YD, Wen W, Fu QL. Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-beta1-Smad2/Smad3 signaling pathway in mice. Mol Immunol. 2019;109:51-7.
42. Royce SG, Mao W, Lim R, Kelly K, Samuel CS. iPSC- and mesenchymoangioblast-derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid. FASEB J. 2019;33(5):6402-11.
43. Pouyanfard S, Meshgin N, Cruz LS, Diggle K, Hashemi H, Pham TV, et al. Human induced pluripotent stem cell-derived macrophages ameliorate liver fibrosis. Stem Cells. 2021;39(12):1701-17.
44. Kuwata F, Ohnishi H, Yamamoto N, Takezawa T, Yamashita M, Okuyama H, et al. Transplantation of human iPS cell-derived airway cells on vitrigel membrane into rat nasal cavity. Tissue Eng Part A. 2021.
45. Bluhmki T, Traub S, Muller AK, Bitzer S, Schruf E, Bammert MT, et al. Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96Transwell air-liquid interface model. Sci Rep. 2021;11(1):17028.
46. Jiang JX, Wellhauser L, Laselva O, Utkina I, Bozoky Z, Gunawardena T, et al. A new platform for high-throughput therapy testing on iPSC-derived lung progenitor cells from cystic fibrosis patients. Stem Cell Reports. 2021;16(11):2825-37.
47. Kerschner JL, Paranjapye A, Yin S, Skander DL, Bebek G, Leir SH, et al. A functional genomics approach to investigate the differentiation of iPSCs into lung epithelium at air-liquid interface. J Cell Mol Med. 2020;24(17):9853-70.
48. Tamo L, Simillion C, Hibaoui Y, Feki A, Gugger M, Prasse A, et al. Gene Network Analysis of Interstitial Macrophages After Treatment with Induced Pluripotent Stem Cells Secretome (iPSC-cm) in the Bleomycin Injured Rat Lung. Stem Cell Rev Rep. 2018;14(3):412-24.
49. Pala L, Giannini S, Rosi E, Cresci B, Scano G, Mohan S, et al. Direct measurement of IGF-I and IGFBP-3 in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis. J Endocrinol Invest. 2001;24(11):856-64.
50. Wynes MW, Frankel SK, Riches DW. IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal. J Leukoc Biol. 2004;76(5):1019-27.
51. Xin X, Hou YT, Li L, Schmiedlin-Ren P, Christman GM, Cheng HL, et al. IGF-I increases IGFBP-5 and collagen alpha1(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. 2004;286(5):G777-83.
52. Dongiovanni P, Valenti L, Rametta R, Daly AK, Nobili V, Mozzi E, et al. Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease. Gut. 2010;59(2):267-73.
2. Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012;21(126):355-61.
3. Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, et al. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res. 2021;22(1):197.
4. Valenzuela C, Torrisi SE, Kahn N, Quaresma M, Stowasser S, Kreuter M. Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme. Respir Res. 2020;21(1):7.
5. Wuyts WA, Wijsenbeek M, Bondue B, Bouros D, Bresser P, Robalo Cordeiro C, et al. Idiopathic Pulmonary Fibrosis: Best Practice in Monitoring and Managing a Relentless Fibrotic Disease. Respiration. 2020;99(1):73-82.
6. Fujimoto H, Kobayashi T, Azuma A. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis. Clin Med Insights Circ Respir Pulm Med. 2015;9(Suppl 1):179-85.
7. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32.
8. Kaunisto J, Salomaa ER, Hodgson U, Kaarteenaho R, Kankaanranta H, Koli K, et al. Demographics and survival of patients with idiopathic pulmonary fibrosis in the FinnishIPF registry. ERJ Open Res. 2019;5(3):00170-2018.
9. Gazdhar A, Grad I, Tamo L, Gugger M, Feki A, Geiser T. The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor. Stem Cell Res Ther. 2014;5(6):123.
10. How CK, Chien Y, Yang KY, Shih HC, Juan CC, Yang YP, et al. Induced pluripotent stem cells mediate the release of interferon gamma-induced protein 10 and alleviate bleomycin-induced lung inflammation and fibrosis. Shock. 2013;39(3):261-70.
11. Zhou Y, Gao Y, Zhang W, Chen Y, Jin M, Yang Z. Exosomes derived from induced pluripotent stem cells suppresses M2-type macrophages during pulmonary fibrosis via miR-302a-3p/TET1 axis. Int Immunopharmacol. 2021;99:108075.
12. Zhou Y, He Z, Gao Y, Zheng R, Zhang X, Zhao L, et al. Induced Pluripotent Stem Cells Inhibit Bleomycin-Induced Pulmonary Fibrosis in Mice through Suppressing TGF-beta1/Smad-Mediated Epithelial to Mesenchymal Transition. Front Pharmacol. 2016;7(1):430.
13. Zhou Y, Zhang Q, Gao Y, Tan M, Zheng R, Zhao L, et al. Induced pluripotent stem cell-conditioned medium suppresses pulmonary fibroblast-to-myofibroblast differentiation via the inhibition of TGF-beta1/Smad pathway. Int J Mol Med. 2018;41(1):473-84.
14. Heukels P, Moor CC, von der Thusen JH, Wijsenbeek MS, Kool M. Inflammation and immunity in IPF pathogenesis and treatment. Respir Med. 2019;147:79-91.
15. Garrett SM, Hsu E, Thomas JM, Pilewski JM, Feghali-Bostwick C. Insulin-like growth factor (IGF)-II- mediated fibrosis in pathogenic lung conditions. PLoS One. 2019;14(11):e0225422.
16. Guiot J, Henket M, Corhay JL, Moermans C, Louis R. Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7. PLoS One. 2017;12(2):e0171344.
17. Hernandez DM, Kang JH, Choudhury M, Andrianifahanana M, Yin X, Limper AH, et al. IPF pathogenesis is dependent upon TGFbeta induction of IGF-1. FASEB J. 2020;34(4):5363-88.
18. Hosono T, Bando M, Mizushina Y, Sata M, Hagiwara K, Sugiyama Y. Inhibitory effects of somatostatin analogue in bleomycin-induced pulmonary fibrosis. Exp Lung Res. 2021;47(6):280-8.
19. Renaud L, da Silveira WA, Takamura N, Hardiman G, Feghali-Bostwick C. Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis. Front Immunol. 2020;11(3):383.
20. Sun W, Jing X, Yang X, Huang H, Luo Q, Xia S, et al. Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation. Aging (Albany N Y). 2021;13(14):18852-69.
21. Xiao H, Huang X, Wang S, Liu Z, Dong R, Song D, et al. Metformin ameliorates bleomycin-induced pulmonary fibrosis in mice by suppressing IGF-1. Am J Transl Res. 2020;12(3):940-9.
22. Kim BN, Ahn DH, Kang N, Yeo CD, Kim YK, Lee KY, et al. TGF-beta induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci Rep. 2020;10(1):10597.
23. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156-72.
24. Bitterman P. Fibroblast-Matrix Cross-Talk in Idiopathic Pulmonary Fibrosis: Cross-Links at the Crossroads. Am J Respir Cell Mol Biol. 2018;58(5):547-8.
25. Ribatti D, Tamma R, Annese T. Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Transl Oncol. 2020;13(6):100773.
26. Liu X, Yun F, Shi L, Li ZH, Luo NR, Jia YF. Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer. Asian Pac J Cancer Prev. 2015;16(15):6201-6.
27. Zhu QQ, Ma C, Wang Q, Song Y, Lv T. The role of TWIST1 in epithelial-mesenchymal transition and cancers. Tumour Biol. 2016;37(1):185-97.
28. Ning X, Zhang K, Wu Q, Liu M, Sun S. Emerging role of Twist1 in fibrotic diseases. J Cell Mol Med. 2018;22(3):1383-91.
29. Ruan W, Ying K. Abnormal expression of IGF-binding proteins, an initiating event in idiopathic pulmonary fibrosis? Pathol Res Pract. 2010;206(8):537-43.
30. Hakuno F, Takahashi SI. IGF1 receptor signaling pathways. J Mol Endocrinol. 2018;61(1):T69-T86.
31. Shaw LM. Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-dependent activation of phosphoinositide 3-OH kinase and promotion of invasion. Mol Cell Biol. 2001;21(15):5082-93.
32. Hua H, Kong Q, Yin J, Zhang J, Jiang Y. Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy. J Hematol Oncol. 2020;13(1):64.
33. Wilker E, Lu J, Rho O, Carbajal S, Beltran L, DiGiovanni J. Role of PI3K/Akt signaling in insulin-like growth factor-1 (IGF-1) skin tumor promotion. Mol Carcinog. 2005;44(2):137-45.
34. Ma X, Bai Y. IGF-1 activates the P13K/AKT signaling pathway via upregulation of secretory clusterin. Mol Med Rep. 2012;6(6):1433-7.
35. Matsunami T, Sato Y, Ariga S, Sato T, Shimomura T, Kashimura H, et al. Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism. 2011;60(6):805-14.
36. Peng CH, Yang YS, Chan KC, Wang CJ, Chen ML, Huang CN. Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase. J Agric Food Chem. 2014;62(40):9736-43.
37. Zhao Q, Zhang CL, Xiang RL, Wu LL, Li L. CTRP15 derived from cardiac myocytes attenuates TGFbeta1-induced fibrotic response in cardiac fibroblasts. Cardiovasc Drugs Ther. 2020;34(5):591-604.
38. Carey BW, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, et al. Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci U S A. 2009;106(1):157-62.
39. Ren Y, Deng CL, Wan WD, Zheng JH, Mao GY, Yang SL. Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation. Mol Med Rep. 2015;11(4):2471-6.
40. Izadi E, Vafashoar F, Jorbozedar P, Safari P, Assarehzadegan MA, Poormoghim H, et al. Effect of Progesterone on Expression of MMP7 and MMP13 in Lungs of Female Mice. Iran J Allergy Asthma Immunol. 2018;17(5):485-9.
41. Zhong H, Fan XL, Fang SB, Lin YD, Wen W, Fu QL. Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-beta1-Smad2/Smad3 signaling pathway in mice. Mol Immunol. 2019;109:51-7.
42. Royce SG, Mao W, Lim R, Kelly K, Samuel CS. iPSC- and mesenchymoangioblast-derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid. FASEB J. 2019;33(5):6402-11.
43. Pouyanfard S, Meshgin N, Cruz LS, Diggle K, Hashemi H, Pham TV, et al. Human induced pluripotent stem cell-derived macrophages ameliorate liver fibrosis. Stem Cells. 2021;39(12):1701-17.
44. Kuwata F, Ohnishi H, Yamamoto N, Takezawa T, Yamashita M, Okuyama H, et al. Transplantation of human iPS cell-derived airway cells on vitrigel membrane into rat nasal cavity. Tissue Eng Part A. 2021.
45. Bluhmki T, Traub S, Muller AK, Bitzer S, Schruf E, Bammert MT, et al. Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96Transwell air-liquid interface model. Sci Rep. 2021;11(1):17028.
46. Jiang JX, Wellhauser L, Laselva O, Utkina I, Bozoky Z, Gunawardena T, et al. A new platform for high-throughput therapy testing on iPSC-derived lung progenitor cells from cystic fibrosis patients. Stem Cell Reports. 2021;16(11):2825-37.
47. Kerschner JL, Paranjapye A, Yin S, Skander DL, Bebek G, Leir SH, et al. A functional genomics approach to investigate the differentiation of iPSCs into lung epithelium at air-liquid interface. J Cell Mol Med. 2020;24(17):9853-70.
48. Tamo L, Simillion C, Hibaoui Y, Feki A, Gugger M, Prasse A, et al. Gene Network Analysis of Interstitial Macrophages After Treatment with Induced Pluripotent Stem Cells Secretome (iPSC-cm) in the Bleomycin Injured Rat Lung. Stem Cell Rev Rep. 2018;14(3):412-24.
49. Pala L, Giannini S, Rosi E, Cresci B, Scano G, Mohan S, et al. Direct measurement of IGF-I and IGFBP-3 in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis. J Endocrinol Invest. 2001;24(11):856-64.
50. Wynes MW, Frankel SK, Riches DW. IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal. J Leukoc Biol. 2004;76(5):1019-27.
51. Xin X, Hou YT, Li L, Schmiedlin-Ren P, Christman GM, Cheng HL, et al. IGF-I increases IGFBP-5 and collagen alpha1(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. 2004;286(5):G777-83.
52. Dongiovanni P, Valenti L, Rametta R, Daly AK, Nobili V, Mozzi E, et al. Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease. Gut. 2010;59(2):267-73.
| Files | ||
| Issue | Vol 21 No 3 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i3.9800 | |
| Keywords | ||
| Idiopathic pulmonary fibrosis Induced pluripotent stem cells Insulin-like growth factor Igf IgfIrs1 protein | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Bayati P, Taherian M, Assarehzadegan M-A, Soleimani M, Poormoghim H, Mojtabavi N. Induced Pluripotent Stem-cells Inhibit Experimental Bleomycin-induced Pulmonary Fibrosis through Regulation of the Insulin-like Growth Factor Signaling. Iran J Allergy Asthma Immunol. 2022;21(3):263-272.
