Asthma is a complex respiratory disease, which is controlled by genetic and environmental factors. Type 2-dominant immune response is responsible for asthma. Decorin (Dcn) and stem cells have modulatory effect on immune system and may control tissue remodeling and asthma pathophysiology. In this study, immunomodulatory effect of transduced induced pluripotent stem cells (iPSCs) with expression of Dcn gene on allergic asthma pathophysiology was evaluated. After transduction of iPSCs with Dcn gene, allergic asthma mice were treated with iPSCs and transduced iPSCs via intrabronchial. Then, airway hyperresponsiveness (AHR), levels of interleukin (IL)-4, IL-5, IL-13, IL-33, total IgE, leukotrienes (LTs) B4, C4, hydroxyproline (HP) content, and transforming growth factor-beta (TGF-β) were measured. Also, lung histopathology study was done. AHR, levels of IL-4, IL-5, IL-13, IL-33, total IgE, LTs B4, C4, TGF-β, HP content, mucus secretion, goblet cell hyperplasia, and eosinophilic inflammation were controlled by iPSCs and transduced iPSCs treatment. Therapeutic effect of iPSCs could control main allergic asthma symptoms and related pathophysiologic mechanisms and the effect can be increased when applied with Dcn expression gene.
AthariSMNasabEMAthariSS.Study effect of Ocimum basilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Revue française d’allergologie2018; 58(7): 489–493.
3.
MaBAthariSSNasabEM, et al. PI3K/AKT/mTOR and TLR4/MyD88/NF-κB signaling inhibitors attenuate pathological mechanisms of allergic asthma. Inflammation2021; 44(5): 1895–1907.
4.
AthariSSAthariSM.The importance of eosinophil, platelet and dendritic cell in asthma. Asian Pac J Trop Dis2014; 4(1): 41–47.
5.
NasabEMAthariSMMotlaghB, et al. Effects of oral administration of Ocimum basilicum on goblet cell hyperplasia and upstream cytokine gene expression in allergic asthma. Revue française d’allergologie2020; 60: 64–68.
6.
JiangJNasabEMAthariSM, et al. Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Physiol Neurobiol2021; 286: 103614.
7.
HajimohammadiBAthariSMAbdollahiM, et al. Oral administration of acrylamide worsens the inflammatory responses in the airways of asthmatic mice through agitation of oxidative stress in the lungs. Front Immunol2020; 11: 1940.
8.
HuangMNasabEMAthariSS.Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J Biol Sci2021; 28: 6957–6962.
9.
AthariSS.Targeting cell signaling in allergic asthma. Signal Transduct Target Ther2019; 4: 45.
10.
QianLNasabEMAthariSM, et al. Mitochondria signaling pathways in allergic asthma. J Investig Med2022; 0: 1–20.
11.
KawakitaNTobaHMiyoshiK, et al. Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration. Stem Cell Res Ther2020; 11: 430.
12.
TropeaKALederEAslamM, et al. Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol2012; 302: 829–837.
13.
GaoGLiQShenH.Effect of Astragali-Cordyceps Mixtura on TGF-β/Smad signal pathway in the lung of asthma airway remodeling. J Ethnopharmacol2009; 125: 68–74.
14.
MarchicaCLPinelliVBorgesM, et al. Ludwig. A role for decorin in a murine model of allergen-induced asthma. Am J Physiol Lung Cell Mol Physiol2011; 300: 863–873.
15.
D’AntoniMLTorregianiCFerraroP, et al. Effects of decorin and biglycan on human airway smooth muscle cell proliferation and apoptosis. Am J Physiol Lung Cell Mol Physiol2008; 294: 764–771.
16.
FustALeBellegoFIozzoRV, et al. Alterations in lung mechanics in decorin-deficient mice. Am J Physiol Lung Cell Mol Physiol2005; 288:159–166.
17.
LiYLiJZhuJ, et al. Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol Ther2007; 15(9): 1616–1622.
18.
SalernoFGPinelliVPiniL, et al. Effect of PEEP on induced constriction is enhanced in decorin-deficient mice. Am J Physiol Lung Cell Mol Physiol2007; 293: 1111–1117.
19.
ReedCCIozzoRV.The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj J2002; 19: 249–255.
20.
TufvessonEWestergren-ThorssonG.Biglycan and decorin induce morphological and cytoskeletal changes involving signalling by the small GTPases RhoA and Rac1 resulting in lung fibroblast migration. J Cell Sci2003; 116: 4857–4864.
21.
MohanRRToveyJCKSharmaA, et al. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo. PLoS One2011; 6(10): e26432.
22.
MarkmannAHausserHSchönherrE, et al. Influence of decorin expression on transforming growth factor-β-mediated collagen gel retraction and biglycan induction. Matrix Biol2000; 19: 631–636.
23.
SchönherrEBroszatMBrandanE, et al. 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 Biophys1998; 355: 241–248.
24.
GreveHBlumbergPSchmidtG, et al. Influence of collagen lattice on the metabolism of small proteoglycan II by cultured fibroblasts. Biochem J1990; 269:149–155.
25.
LeeCGKangHRHomerRJ, et al. Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling. Proc Am Thorac Soc2006; 3: 418–423.
26.
AbbahSAThomasDBrowneS, et al. Co-transfection of decorin and interleukin-10 modulates profibrotic extracellular matrix gene expression in human tenocyte culture. Sci Rep2016; 6: 20922.
27.
DochevaDMüllerSMajewskiM, et al. Biologics for tendon repair. Adv Drug Deliv Rev2015; 84: 222–239.
28.
PohlersDBrenmoehlJLöfflerI, et al. TGF-beta and fibrosis in different organs – molecular pathway imprints. Biochim Biophys Acta2009; 1792: 746–756.
29.
CutroneoK.TGF-beta-induced fibrosis and SMAD signaling: Oligo decoys as natural therapeutics for inhibition of tissue fibrosis and scarring. Wound Repair Regen2007; 15: S54–S60.
30.
FarhatYMAl-MalikiAAChenT, et al. Gene expression analysis of the pleiotropic effects of TGF-β 1 in an in vitro model of flexor tendon healing. PLoS One2012; 7: e51411.
31.
KenyonNWardRMcGrewG, et al. TGF-beta1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax2003; 58: 772–777.
32.
ZhangWGeYChengQ, et al. Decorin is a pivotal effector in the extracellular matrix and tumour microenvironment. Oncotarget2018; 9: 5480–5491.
33.
RuoslahtiEYamaguchiY.Proteoglycans as modulators of growth factor activities. Cell1991; 64: 867–869.
34.
YamaguchiYMannDMRuoslahtiE.Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature1990; 346: 281–284.
35.
JiangNZhangQChauMKM, et al. Anti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis. EBioMedicine2020; 52: 102661.
36.
NeillTSchaeferLIozzoRV.Decorin as a multivalent therapeutic agent against cancer. Adv Drug Deliv Rev2016; 97: 174–185.
37.
BiXLYangW.Biological functions of decorin in cancer. Chin J Cancer2013; 32: 266–269.
38.
GoldoniSHumphriesANyströmA, et al. Decorin is a novel antagonistic ligand of the Met receptor. J Cell Biol2009; 185: 743–754.
39.
KhanGAGirishGVLalaN, et al. Decorin is a novel VEGFR- 2-binding antagonist for the human extravillous trophoblast. Mol Endocrinol2011; 25: 1431–1443.
40.
BaghyKHorváthZRegősE, et al. Decorin interferes with platelet-derived growth factor receptor signaling in experimental hepatocarcinogenesis. FEBS J2013; 280: 2150–2164.
41.
MohanRRGuptaRMehanMK, et al. Decorin transfection suppresses profibrogenic genes and myofibroblast formation in human corneal fibroblasts. Exper Eye Res2010; 91: 238–245.
42.
AllawadhiPSinghVKhuranaI, et al. Decorin as a possible strategy for the amelioration of COVID-19. Med Hypotheses2021; 152: 110612.
43.
ChenSYoungMFChakravartiS, et al. Interclass small leucine-rich repeat proteoglycan interactions regulate collagen fibrillogenesis and corneal stromal assembly. Matrix Biol2014; 35: 103–11.
44.
RobinsonPSHuangTFKazamE, et al. Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice. J Biomech Eng2005; 127: 181–185.
45.
MohanRRTandonASharmaA, et al. Significant inhibition of corneal scarring in vivo with tissue-selective, targeted AAV5 decorin gene therapy. IOVS2011; 52(7): 4833–4841.
46.
FerdousZWeiVMIozzoR, et al. Decorin transforming growth factor-interaction regulates matrix organization and mechanical characteristics of three-dimensional collagen matrices. J Biol Chem2007; 7(282): 35887–35898.
47.
KalamajskiSOldbergA.The role of small leucine-rich proteoglycans in collagen fibrillogenesis. Matrix Biol2010; 29: 248–253.
SulochanaKNFanHJoisS, et al. Peptides derived from human decorin leucine-rich repeat 5 inhibit angiogenesis. J Biol Chem2005; 280: 27935–27948.
50.
SharmaABettisDICowdenJW, et al. Localization of angiotensin converting enzyme in rabbit cornea and its role in controlling corneal angiogenesis in vivo. Mol Vis2010; 16: 720–728.
51.
PearsonDSasseJ.Differential regulation of biglycan and decorin by retinoic acid in bovine chondrocytes. J Biol Chem1992; 267: 25364–25370.
52.
ReedCCGauldieJIozzoRV.Suppression of tumorigenicity by adenovirus-mediated gene transfer of decorin. Oncogene2002; 21: 3688–3695.
53.
GiriNHydeDMBraunRK, et al. Antifibrotic effect of decorin in a bleomycin hamster model of lung fibrosis. Biochem Pharmacol1997; 54: 1205–1216.
54.
KehletSNBagerCLWillumsenN, et al. Cathepsin-S degraded decorin are elevated in fibrotic lung disorders – development and biological validation of a new serum biomarker. BMC Pulm Med2017; 17:110
55.
ChanBCLLamCWKTamL-S, et al. IL33: Roles in allergic inflammation and therapeutic perspectives. Front Immunol2019; 10: 364.
56.
Saikumar JayalathaAKHesseLKetelaarME, et al. The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention. Pharmacol Ther2021; 225: 107847.
57.
WarrenKJPooleJASweeterJM, et al. Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation. Respir Res2021; 22: 206.
58.
BorishLSteinkeJW.Interleukin-33 in asthma: how big of a role does it play?Curr Allergy Asthma Rep2011; 11(1): 7–11.
