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Pivotal role of lnk adaptor protein in endothelial progenitor cell biology for vascular regeneration.
Circ Res. 2009 Apr 24; 104(8):969-77.CircR

Abstract

Despite the fact that endothelial progenitor cells (EPCs) are important for postnatal neovascularization, their origins, differentiation, and modulators are not clear. Here, we demonstrate that Lnk, a negative regulator of hematopoietic stem cell proliferation, controls endothelial commitment of c-kit(+)/Sca-1(+)/Lineage(-) (KSL) subpopulations of bone marrow cells. The results of EPC colony-forming assays reveal that small (primitive) EPC colony formation by CD34(-) KSLs and large (definitive) EPC colony formation by CD34((dim)) KSLs are more robust in lnk(-/-) mice. In hindlimb ischemia, perfusion recovery is augmented in lnk(-/-) mice through enhanced proliferation and mobilization of EPCs via c-Kit/stem cell factor. We found that Lnk-deficient EPCs are more potent actors than resident cells in hindlimb perfusion recovery and ischemic neovascularization, mainly via the activity of bone marrow-EPCs. Similarly, lnk(-/-) mice show augmented retinal neovascularization and astrocyte network maturation without an increase in indicators of pathogenic angiogenesis in an in vivo model of retinopathy. Taken together, our results provide strong evidence that Lnk regulates bone marrow-EPC kinetics in vascular regeneration. Selective targeting of Lnk may be a safe and effective strategy to augment therapeutic neovascularization by EPC transplantation.

Authors+Show Affiliations

Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19325148

Citation

Kwon, Sang-Mo, et al. "Pivotal Role of Lnk Adaptor Protein in Endothelial Progenitor Cell Biology for Vascular Regeneration." Circulation Research, vol. 104, no. 8, 2009, pp. 969-77.
Kwon SM, Suzuki T, Kawamoto A, et al. Pivotal role of lnk adaptor protein in endothelial progenitor cell biology for vascular regeneration. Circ Res. 2009;104(8):969-77.
Kwon, S. M., Suzuki, T., Kawamoto, A., Ii, M., Eguchi, M., Akimaru, H., Wada, M., Matsumoto, T., Masuda, H., Nakagawa, Y., Nishimura, H., Kawai, K., Takaki, S., & Asahara, T. (2009). Pivotal role of lnk adaptor protein in endothelial progenitor cell biology for vascular regeneration. Circulation Research, 104(8), 969-77. https://doi.org/10.1161/CIRCRESAHA.108.192856
Kwon SM, et al. Pivotal Role of Lnk Adaptor Protein in Endothelial Progenitor Cell Biology for Vascular Regeneration. Circ Res. 2009 Apr 24;104(8):969-77. PubMed PMID: 19325148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pivotal role of lnk adaptor protein in endothelial progenitor cell biology for vascular regeneration. AU - Kwon,Sang-Mo, AU - Suzuki,Takahiro, AU - Kawamoto,Atsuhiko, AU - Ii,Masaaki, AU - Eguchi,Masamichi, AU - Akimaru,Hiroshi, AU - Wada,Mika, AU - Matsumoto,Tomoyuki, AU - Masuda,Haruchika, AU - Nakagawa,Yoshihiro, AU - Nishimura,Hiromi, AU - Kawai,Kenji, AU - Takaki,Satoshi, AU - Asahara,Takayuki, Y1 - 2009/03/26/ PY - 2009/3/28/entrez PY - 2009/3/28/pubmed PY - 2009/5/8/medline SP - 969 EP - 77 JF - Circulation research JO - Circ Res VL - 104 IS - 8 N2 - Despite the fact that endothelial progenitor cells (EPCs) are important for postnatal neovascularization, their origins, differentiation, and modulators are not clear. Here, we demonstrate that Lnk, a negative regulator of hematopoietic stem cell proliferation, controls endothelial commitment of c-kit(+)/Sca-1(+)/Lineage(-) (KSL) subpopulations of bone marrow cells. The results of EPC colony-forming assays reveal that small (primitive) EPC colony formation by CD34(-) KSLs and large (definitive) EPC colony formation by CD34((dim)) KSLs are more robust in lnk(-/-) mice. In hindlimb ischemia, perfusion recovery is augmented in lnk(-/-) mice through enhanced proliferation and mobilization of EPCs via c-Kit/stem cell factor. We found that Lnk-deficient EPCs are more potent actors than resident cells in hindlimb perfusion recovery and ischemic neovascularization, mainly via the activity of bone marrow-EPCs. Similarly, lnk(-/-) mice show augmented retinal neovascularization and astrocyte network maturation without an increase in indicators of pathogenic angiogenesis in an in vivo model of retinopathy. Taken together, our results provide strong evidence that Lnk regulates bone marrow-EPC kinetics in vascular regeneration. Selective targeting of Lnk may be a safe and effective strategy to augment therapeutic neovascularization by EPC transplantation. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/19325148/Pivotal_role_of_lnk_adaptor_protein_in_endothelial_progenitor_cell_biology_for_vascular_regeneration_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.108.192856?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -