Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells
Authors: Kakali Sarkar
Sergio Rey
Guy P Marti
Gregg L Semenza
Frank J Gonzalez
Amanda V Cardona
Lixin Liu
Karen Fox-Talbot
John W Harmon
Xianjie Zhang
Junkai Du
Raul Sebastian
Frank Lay
Yee Sun Tan
Journal: Cardiovascular Research (2012)
Discipline: CLINICAL MEDICINE
Keywords: Hypoxia-inducible factor 1; HIF-1; vascularization; angiogenic factors; endothelial cells
Affiliations: Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract:  Aims: Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of HIF-1Œ± and HIF-1Œ≤ subunits. HIF-1 is known to promote tissue vascularization by activating the transcription of genes encoding angiogenic factors, which bind to receptors on endothelial cells (ECs) and bone marrow-derived angiogenic cells (BMDACs). In this study, we analysed whether HIF-1 activity in the responding ECs and BMDACs is also required for cutaneous vascularization during burn wound healing. Methods and results: We generated mice with floxed alleles at the Hif1a or Arnt locus encoding HIF-1Œ± and HIF-1Œ≤, respectively. Expression of Cre recombinase was driven by the Tie2 gene promoter, which is expressed in ECs and bone marrow cells. Tie2Cre(+) and Tie2Cre(-) mice were subjected to burn wounds of reproducible diameter and depth. Deficiency of HIF-1Œ± or HIF-1Œ≤ in Tie2-lineage cells resulted in delayed wound closure, reduced vascularization, decreased cutaneous blood flow, impaired BMDAC mobilization, and decreased BMDAC homing to burn wounds. Conclusion: HIF-1 activity in Tie2-lineage cells is required for the mobilization and homing of BMDACs to cutaneous burn wounds and for the vascularization of burn wound tissue. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: The inset shown in the panel for the Arnt f f- Tie2Cre+ mouse appears to also be visible in the panel for the Arnt f f -Tie2Cre- mouse. Could the authors please check?  , 
 This hardly appears to be a major issue. The inset in question ( high magnification of vascular structure ) was placed probably on the wrong panel (should have been top left, where it clearly came from). , 
 https: academic.oup.com cardiovascres advance-article doi 10.1093 cvr cvab020 6124096 **Corrigendum to**: Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells [Cardiovasc Res. 2012;93(1):162-9; doi: 10.1093 cvr cvr282] The authors have contacted the Editorial Office to request a correction to Figure 3 of this manuscript. The two insets, which are located on the right side of Fig. 3A, were not derived from the larger photomicrographs that they overlay, but rather are magnified images of representative vascular structures in the dermis that stained with the CD31 and u03b1SMA antibodies, respectively. Although there is no error involved, the authors would like to clarify and have provided a new figure in which the images are presented in a separate column. This change does not affect the overall scientific message of the paper. The figure legend for Figure 3 has also been updated: This matter was investigated by the ESC Journals Family Ethics Committee, which recommended this resolution.  , 
 #2  The inset in question ( high magnification of vascular structure ) was placed probably on the wrong panel (should have been top left, where it clearly came from). Affirmative. 2021 correction. https: academic.oup.com cardiovascres advance-article doi 10.1093 cvr cvab020 6124096 Corrigendum to: Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells [Cardiovasc Res. 2012;93(1):162-9; doi: 10.1093 cvr cvr282] The authors have contacted the Editorial Office to request a correction to Figure 3 of this manuscript. The two insets, which are located on the right side of Fig. 3A, were not derived from the larger photomicrographs that they overlay, but rather are magnified images of representative vascular structures in the dermis that stained with the CD31 and u03b1SMA antibodies, respectively. Although there is no error involved, the authors would like to clarify and have provided a new figure in which the images are presented in a separate column. This change does not affect the overall scientific message of the paper. The figure legend for Figure 3 has also been updated: This matter was investigated by the ESC Journals Family Ethics Committee, which recommended this resolution. ,