Activation of Notch1 Signaling Alleviates Dysfunction of Bone Marrow-derived Mesenchymal Stem Cells Induced by Cigarette Smoke Extract

Overview

Journal Int J Chron Obstruct Pulmon Dis

Publisher Dove Medical Press

Specialty Pulmonary Medicine

Date 2017 Nov 16

PMID 29138545

Citations 11

Authors

Yi Cheng

Wen Gu

Guorui Zhang

Xiaoming Li

Xuejun Guo

Affiliations

Soon will be listed here.

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered attractive therapeutic agents for the treatment of COPD. However, little is known about the impact of Notch on the proliferation, migration, and survival of MSCs in a cigarette smoke (CS) microenvironment. Here, we used CS extract to mimic the CS microenvironment in vitro, with the intention to investigate the effect of Notch in regulating proliferation, migration, and survival of BM-MSCs. Rat bone marrow mesenchymal stem cells were infected with lentivirus vector containing the intracellular domain of Notch1 (N1ICD) and challenged with CS extract. Cell proliferation was detected by Ki67 staining and expression of cell cycle-related proteins. A transwell assay was used to measure cell migration and the expression of apoptotic proteins was examined. The proliferation of BM-MSCs overexpressing N1ICD significantly increased. Consistently, levels of cyclin D1, p-Rb, and E2F-1 increased in N1ICD overexpressing cells. N1ICD overexpression also increased cell migration compared with the control group. N1ICD overexpression equilibrated the expression of Bax and Bcl-2, and blocked caspase-3 cleavage, contributing to the inhibition of apoptosis. Moreover, blockade of the PI3K/Akt pathway suppressed the aforementioned cytoprotective effects of N1ICD. In conclusion, activation of Notch signaling improved proliferation, migration, and survival of BM-MSCs in a CS microenvironment partly through the PI3K/Akt pathway.

Citing Articles

Exposure to 16 Hz Pulsed Electromagnetic Fields Protect the Structural Integrity of Primary Cilia and Associated TGF-β Signaling in Osteoprogenitor Cells Harmed by Cigarette Smoke.

Chen Y, Aspera-Werz R, Menger M, Falldorf K, Ronniger M, Stacke C Int J Mol Sci. 2021; 22(13).

PMID: 34210094 PMC: 8268780. DOI: 10.3390/ijms22137036.

Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels.

Weiss D, Segal K, Casaburi R, Hayes J, Tashkin D Respir Res. 2021; 22(1):142.

PMID: 33964910 PMC: 8106850. DOI: 10.1186/s12931-021-01734-8.

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.

Damasceno P, de Santana T, Santos G, Orge I, Silva D, Albuquerque J Front Cell Dev Biol. 2020; 8:737.

PMID: 32974331 PMC: 7471932. DOI: 10.3389/fcell.2020.00737.

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways.

Dang X, He B, Ning Q, Liu Y, Guo J, Niu G Respir Res. 2020; 21(1):95.

PMID: 32321531 PMC: 7178609. DOI: 10.1186/s12931-020-01358-4.

Oestrogen Receptor β Activation Protects Against Myocardial Infarction via Notch1 Signalling.

Du M, Shan J, Feng A, Schmull S, Gu J, Xue S Cardiovasc Drugs Ther. 2020; 34(2):165-178.

PMID: 32157565 PMC: 7223456. DOI: 10.1007/s10557-020-06949-3.

References

Lee J, Gupta N, Serikov V, Matthay M . Potential application of mesenchymal stem cells in acute lung injury. Expert Opin Biol Ther. 2009; 9(10):1259-70. PMC: 2852252. DOI: 10.1517/14712590903213651. View

Gehmert S, Sadat S, Song Y, Yan Y, Alt E . The anti-apoptotic effect of IGF-1 on tissue resident stem cells is mediated via PI3-kinase dependent secreted frizzled related protein 2 (Sfrp2) release. Biochem Biophys Res Commun. 2008; 371(4):752-5. DOI: 10.1016/j.bbrc.2008.04.151. View

Kern S, Eichler H, Stoeve J, Kluter H, Bieback K . Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24(5):1294-301. DOI: 10.1634/stemcells.2005-0342. View

Huh J, Kim S, Lee J, Lee J, Van Ta Q, Kim M . Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am J Physiol Lung Cell Mol Physiol. 2011; 301(3):L255-66. DOI: 10.1152/ajplung.00253.2010. View

Jafari N, Hintzen R . The association between cigarette smoking and multiple sclerosis. J Neurol Sci. 2011; 311(1-2):78-85. DOI: 10.1016/j.jns.2011.09.008. View

Chadwick N, Nostro M, Baron M, Mottram R, Brady G, Buckle A . Notch signaling induces apoptosis in primary human CD34+ hematopoietic progenitor cells. Stem Cells. 2006; 25(1):203-10. DOI: 10.1634/stemcells.2005-0303. View

Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O . HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003; 31(10):890-6. DOI: 10.1016/s0301-472x(03)00110-3. View

Nair P, Somasundaram K, Krishna S . Activated Notch1 inhibits p53-induced apoptosis and sustains transformation by human papillomavirus type 16 E6 and E7 oncogenes through a PI3K-PKB/Akt-dependent pathway. J Virol. 2003; 77(12):7106-12. PMC: 156194. DOI: 10.1128/jvi.77.12.7106-7112.2003. View

Sun X, Gao X, Zhou L, Sun L, Lu C . PDGF-BB-induced MT1-MMP expression regulates proliferation and invasion of mesenchymal stem cells in 3-dimensional collagen via MEK/ERK1/2 and PI3K/AKT signaling. Cell Signal. 2013; 25(5):1279-87. DOI: 10.1016/j.cellsig.2013.01.029. View

10.

Chen Y, Lan Y, Chen L, Huang T, Choo K, Cheng W . Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model. Cell Stress Chaperones. 2015; 20(6):979-89. PMC: 4595438. DOI: 10.1007/s12192-015-0627-7. View

11.

Carnevali S, Petruzzelli S, Longoni B, Vanacore R, Barale R, Cipollini M . Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2003; 284(6):L955-63. DOI: 10.1152/ajplung.00466.2001. View

12.

Zhang W, He L, Shi X, Wu S, Zhang B, Mei L . Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in rats with chronic obstructive pulmonary disease. Respir Res. 2014; 15:33. PMC: 3987841. DOI: 10.1186/1465-9921-15-33. View

13.

Alfaro M, Vincent A, Saraswati S, Thorne C, Hong C, Lee E . sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. J Biol Chem. 2010; 285(46):35645-53. PMC: 2975189. DOI: 10.1074/jbc.M110.135335. View

14.

Wang L, Wang Y, Hu X, Zhang B, Dou G, He F . Notch-RBP-J signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of CXCR4 expression in mice. PLoS One. 2009; 4(10):e7572. PMC: 2762521. DOI: 10.1371/journal.pone.0007572. View

15.

Palange P, Testa U, Huertas A, Calabro L, Antonucci R, Petrucci E . Circulating haemopoietic and endothelial progenitor cells are decreased in COPD. Eur Respir J. 2006; 27(3):529-41. DOI: 10.1183/09031936.06.00120604. View

16.

Iso T, Kedes L, Hamamori Y . HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol. 2003; 194(3):237-55. DOI: 10.1002/jcp.10208. View

17.

Kopan R, Ilagan M . The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009; 137(2):216-33. PMC: 2827930. DOI: 10.1016/j.cell.2009.03.045. View

18.

Baldi A, De Falco M, De Luca L, Cottone G, Paggi M, Nickoloff B . Characterization of tissue specific expression of Notch-1 in human tissues. Biol Cell. 2004; 96(4):303-11. DOI: 10.1016/j.biolcel.2004.01.005. View

19.

Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H . G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med. 2005; 11(3):305-11. DOI: 10.1038/nm1199. View

20.

Sade H, Krishna S, Sarin A . The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells. J Biol Chem. 2003; 279(4):2937-44. DOI: 10.1074/jbc.M309924200. View