MicroRNA126 Contributes to Granulocyte Colony-stimulating Factor-induced Hematopoietic Progenitor Cell Mobilization by Reducing the Expression of Vascular Cell Adhesion Molecule 1

Overview

Journal Haematologica

Specialty Hematology

Date 2012 Jan 25

PMID 22271895

Citations 34

Authors

Ombretta Salvucci

Kan Jiang

Paola Gasperini

Dragan Maric

Jinfang Zhu

Shuhei Sakakibara

Georgina Espigol-Frigole

Shushang Wang

Giovanna Tosato

Affiliations

Soon will be listed here.

Abstract

Background: Mobilization of hematopoietic stem/progenitor cells from the bone marrow to the peripheral blood by granulocyte colony-stimulating factor is the primary means to acquire stem cell grafts for hematopoietic cell transplantation. Since hematopoietic stem/progenitor cells represent a minority of all blood cells mobilized by granulocyte colony-stimulating factor, the underlying mechanisms need to be understood in order to develop selective drugs.

Design And Methods: We analyzed phenotypic, biochemical and genetic changes in bone marrow cell populations from granulocyte colony-stimulating factor-mobilized and control mice, and linked such changes to effective mobilization of hematopoietic stem/progenitor cells.

Results: We show that granulocyte colony-stimulating factor indirectly reduces expression of surface vascular cell adhesion molecule 1 on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells by promoting the accumulation of microRNA-126 (miR126)-containing microvescicles in the bone marrow extracellular compartment. We found that hematopoietic stem/progenitor cells, stromal cells and endothelial cells readily incorporate these miR126-loaded microvescicles, and that miR126 represses vascular cell adhesion molecule 1 expression on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells. In line with this, miR126-null mice displayed a reduced mobilization response to granulocyte colony-stimulating factor.

Conclusions: Our results implicate miR126 in the regulation of hematopoietic stem/progenitor cell trafficking between the bone marrow and peripheral sites, clarify the role of vascular cell adhesion molecule 1 in granulocyte colony-stimulating factor-mediated mobilization, and have important implications for improved approaches to selective mobilization of hematopoietic stem/progenitor cells.

Citing Articles

Involvement of circulating microRNAs in the pathogenesis of atherosclerosis in young patients with obesity.

Mazgutova N, Witvrouwen I, Czippelova B, Turianikova Z, cernanova Krohova J, Kosutova P Physiol Res. 2025; 73(S3):S755-S769.

PMID: 39808176 PMC: 11827058. DOI: 10.33549/physiolres.935467.

Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells.

Ruminski P, Rettig M, Dipersio J Biomolecules. 2024; 14(8).

PMID: 39199390 PMC: 11353233. DOI: 10.3390/biom14081003.

The role of the hematopoietic stem/progenitor cells-derived extracellular vesicles in hematopoiesis.

Fathi E, Valipour B, Jafari S, Kazemi A, Montazersaheb S, Farahzadi R Heliyon. 2024; 10(15):e35051.

PMID: 39157371 PMC: 11327835. DOI: 10.1016/j.heliyon.2024.e35051.

Non-Classical Intercellular Communications: Basic Mechanisms and Roles in Biology and Medicine.

Polyakova N, Kalashnikova M, Belyavsky A Int J Mol Sci. 2023; 24(7).

PMID: 37047428 PMC: 10095225. DOI: 10.3390/ijms24076455.

Emerging roles of extracellular vesicles in normal and malignant hematopoiesis.

Sun G, Gu Q, Zheng J, Cheng H, Cheng T J Clin Invest. 2022; 132(18).

PMID: 36106632 PMC: 9479752. DOI: 10.1172/JCI160840.

References

Ulyanova T, Priestley G, Nakamoto B, Jiang Y, Papayannopoulou T . VCAM-1 ablation in nonhematopoietic cells in MxCre+ VCAM-1f/f mice is variable and dictates their phenotype. Exp Hematol. 2007; 35(4):565-71. PMC: 1905849. DOI: 10.1016/j.exphem.2007.01.031. View

Levesque J, Hendy J, Takamatsu Y, Simmons P, Bendall L . Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003; 111(2):187-96. PMC: 151860. DOI: 10.1172/JCI15994. View

Peche H, Heslan M, Usal C, Amigorena S, Cuturi M . Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection. Transplantation. 2003; 76(10):1503-10. DOI: 10.1097/01.TP.0000092494.75313.38. View

Eash K, Greenbaum A, Gopalan P, Link D . CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest. 2010; 120(7):2423-31. PMC: 2898597. DOI: 10.1172/JCI41649. View

Semerad C, Christopher M, Liu F, Short B, Simmons P, Winkler I . G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood. 2005; 106(9):3020-7. PMC: 1895331. DOI: 10.1182/blood-2004-01-0272. View

Pelus L, Fukuda S . Chemokine-mobilized adult stem cells; defining a better hematopoietic graft. Leukemia. 2007; 22(3):466-73. PMC: 2814589. DOI: 10.1038/sj.leu.2405021. View

Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B . Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009; 2(100):ra81. DOI: 10.1126/scisignal.2000610. View

Zohren F, Toutzaris D, Klarner V, Hartung H, Kieseier B, Haas R . The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood. 2008; 111(7):3893-5. DOI: 10.1182/blood-2007-10-120329. View

Rankin S . The bone marrow: a site of neutrophil clearance. J Leukoc Biol. 2010; 88(2):241-51. DOI: 10.1189/jlb.0210112. View

10.

Eash K, Means J, White D, Link D . CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood. 2009; 113(19):4711-9. PMC: 2680371. DOI: 10.1182/blood-2008-09-177287. View

11.

Liu F, Poursine-Laurent J, Link D . Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF. Blood. 2000; 95(10):3025-31. View

12.

McCormick P, Segarra M, Gasperini P, Gulino A, Tosato G . Impaired recruitment of Grk6 and beta-Arrestin 2 causes delayed internalization and desensitization of a WHIM syndrome-associated CXCR4 mutant receptor. PLoS One. 2009; 4(12):e8102. PMC: 2779657. DOI: 10.1371/journal.pone.0008102. View

13.

Vermeulen M, Le Pesteur F, Gagnerault M, Mary J, Sainteny F, Lepault F . Role of adhesion molecules in the homing and mobilization of murine hematopoietic stem and progenitor cells. Blood. 1998; 92(3):894-900. View

14.

De La Luz Sierra M, Gasperini P, McCormick P, Zhu J, Tosato G . Transcription factor Gfi-1 induced by G-CSF is a negative regulator of CXCR4 in myeloid cells. Blood. 2007; 110(7):2276-85. PMC: 1988943. DOI: 10.1182/blood-2007-03-081448. View

15.

A Ryan M, Nattamai K, Xing E, Schleimer D, Daria D, Sengupta A . Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization. Nat Med. 2010; 16(10):1141-6. PMC: 4464748. DOI: 10.1038/nm.2217. View

16.

Nakayama T, Mutsuga N, Tosato G . Effect of fibroblast growth factor 2 on stromal cell-derived factor 1 production by bone marrow stromal cells and hematopoiesis. J Natl Cancer Inst. 2007; 99(3):223-35. DOI: 10.1093/jnci/djk031. View

17.

Papayannopoulou T, Nakamoto B . Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci U S A. 1993; 90(20):9374-8. PMC: 47570. DOI: 10.1073/pnas.90.20.9374. View

18.

Caby M, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C . Exosomal-like vesicles are present in human blood plasma. Int Immunol. 2005; 17(7):879-87. DOI: 10.1093/intimm/dxh267. View

19.

Dipersio J, Stadtmauer E, Nademanee A, Micallef I, Stiff P, Kaufman J . Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009; 113(23):5720-6. DOI: 10.1182/blood-2008-08-174946. View

20.

Ulyanova T, Scott L, Priestley G, Jiang Y, Nakamoto B, Koni P . VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin. Blood. 2005; 106(1):86-94. PMC: 1895134. DOI: 10.1182/blood-2004-09-3417. View