Heme Oxygenase-1 Accelerates Cutaneous Wound Healing in Mice

Grochot-Przęczek, Anna; Lach, Radosław; Mis, Jacek; Skrzypek, Klaudia; Gozdecka, Malgorzata; Sroczyńska, Patrycja; Dubiel, M.; Rutkowski, A.; Kozakowska, Magdalena; Загорска, Анна; Walczynski, Jacek; Waś, Halina; Kotlinowski, Jerzy; Drukała, Justyna; Kurowski, Krzysztof; Kiéda, Claudine; Hérault, Yann; Dulak, Józef; Józkowicz, Alicja

doi:10.1371/journal.pone.0005803

Cited by 119 publications

(130 citation statements)

References 78 publications

(109 reference statements)

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…Hmox1 -/ -mice produce higher levels of the angiogenic inhibitors soluble VEGF and soluble endoglin (30). They also have impaired wound healing and wound neovascularization compared with wild-type littermates (57). Hmox1 deficiency is associated with more damage from myocardial ischemia-reperfusion injury (77,197).…”

Section: As Mentioned Earlier Hmox1mentioning

confidence: 99%

New Insights into Intracellular Locations and Functions of Heme Oxygenase-1

Dunn

Midwinter²,

Ni³

et al. 2014

Antioxidants & Redox Signaling

127

116

View full text Add to dashboard Cite

Significance: Heme oxygenase-1 (HMOX1) plays a critical role in the protection of cells, and the inducible enzyme is implicated in a spectrum of human diseases. The increasing prevalence of cardiovascular and metabolic morbidities, for which current treatment approaches are not optimal, emphasizes the necessity to better understand key players such as HMOX1 that may be therapeutic targets. Recent Advances: HMOX1 is a dynamic protein that can undergo post-translational and structural modifications which modulate HMOX1 function. Moreover, trafficking from the endoplasmic reticulum to other cellular compartments, including the nucleus, highlights that HMOX1 may play roles other than the catabolism of heme. Critical Issues: The ability of HMOX1 to be induced by a variety of stressors, in an equally wide variety of tissues and cell types, represents an obstacle for the therapeutic exploitation of the enzyme. Any capacity to modulate HMOX1 in cardiovascular and metabolic diseases should be tempered with an appreciation that HMOX1 may have an impact on cancer. Moreover, the potential for heme catabolism end products, such as carbon monoxide, to amplify the HMOX1 stress response should be considered. Future Directions: A more complete understanding of HMOX1 modifications and the properties that they impart is necessary. Delineating these parameters will provide a clearer picture of the opportunities to modulate HMOX1 in human disease. Antioxid. Redox Signal. 20: 1723-1742.

show abstract

Section: As Mentioned Earlier Hmox1mentioning

confidence: 99%

New Insights into Intracellular Locations and Functions of Heme Oxygenase-1

Dunn

Midwinter²,

Ni³

et al. 2014

Antioxidants & Redox Signaling

127

116

View full text Add to dashboard Cite

show abstract

“…Lung-specific HO-1 expression also conferred anti-inflammatory protection against acute hypoxic and LPS challenge (71). Recent studies using keratinocyte-specific human HO-1 transgenic mice indicate that targeted overexpression of HO-1 in the skin promoted cutaneous wound healing and neovascularization (72). These studies, taken together, have implicated HO-1 as a critical defense against tissue injury.…”

Section: Ho-1 In Homeostasis and Tissue Protectionmentioning

confidence: 99%

Heme Oxygenase-1/Carbon Monoxide

Ryter

Choi

2009

Am J Respir Cell Mol Biol

253

View full text Add to dashboard Cite

Heme oxygenase-1 (HO-1), a ubiquitous inducible stress-response protein, serves a major metabolic function in heme turnover. HO activity cleaves heme to form biliverdin-IXa, carbon monoxide (CO), and iron. Genetic experiments have revealed a central role for HO-1 in tissue homeostasis, protection against oxidative stress, and in the pathogenesis of disease. Four decades of research have witnessed not only progress in elucidating the molecular mechanisms underlying the regulation and function of this illustrious enzyme, but also have opened remarkable translational applications for HO-1 and its reaction products. CO, once regarded as a metabolic waste, can act as an endogenous mediator of cellular signaling and vascular function. Exogenous application of CO by inhalation or pharmacologic delivery can confer cytoprotection in preclinical models of lung/vascular injury and disease, based on anti-apoptotic, antiinflammatory, and anti-proliferative properties. The bile pigments, biliverdin and bilirubin, end products of heme degradation, have also shown potential as therapeutics in vascular disease based on anti-inflammatory and anti-proliferative activities. Further translational and clinical trials research will unveil whether the HO-1 system or any of its reaction products can be successfully applied as molecular medicine in human disease.

show abstract

“…HO-1 degrades heme to carbon monoxide (CO), ferrous ion, and biliverdin, which is subsequently reduced to bilirubin by biliverdin reductase (44). HO-1 can be induced on injury (22), augmenting the tissue regeneration (54). Proangiogenic properties of HO-1 were confirmed in various research models, both in vitro and in vivo (40).…”

Section: Introductionmentioning

confidence: 98%

Heme Oxygenase-1 Is Required for Angiogenic Function of Bone Marrow-Derived Progenitor Cells: Role in Therapeutic Revascularization

Grochot-Przęczek

Kotlinowski²,

Kozakowska³

et al. 2014

Antioxidants & Redox Signaling

Self Cite

View full text Add to dashboard Cite

Aims: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that can be down-regulated in diabetes. Its importance for mature endothelium has been described, but its role in proangiogenic progenitors is not well known. We investigated the effect of HO-1 on the angiogenic potential of bone marrow-derived cells (BMDCs) and on blood flow recovery in ischemic muscle of diabetic mice. BMDCs revealed the attenuated up-regulation of proangiogenic genes in response to hypoxia. Heterozygous HO-1 +/ -diabetic mice subjected to hind limb ischemia exhibited reduced local expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), stromal cell-derived factor 1 (SDF-1), VEGFR-1, VEGFR-2, and CXCR-4. This was accompanied by impaired revascularization of ischemic muscle, despite a strong mobilization of bone marrow-derived proangiogenic progenitors (Sca-1 + CXCR-4 + ) into peripheral blood. Blood flow recovery could be rescued by local injections of conditioned media harvested from BMDCs, but not by an injection of cultured BMDCs. Innovation: This is the first report showing that HO-1 haploinsufficiency impairs tissue revascularization in diabetes and that proangiogenic in situ response, not progenitor cell mobilization, is important for blood flow recovery. Conclusions: HO-1 is necessary for a proper proangiogenic function of BMDCs. A low level of HO-1 in hyperglycemic mice decreases restoration of perfusion in ischemic muscle, which can be rescued by a local injection of conditioned media from cultured

show abstract

Heme Oxygenase-1 Accelerates Cutaneous Wound Healing in Mice

Cited by 119 publications

References 78 publications

New Insights into Intracellular Locations and Functions of Heme Oxygenase-1

New Insights into Intracellular Locations and Functions of Heme Oxygenase-1

Heme Oxygenase-1/Carbon Monoxide

Heme Oxygenase-1 Is Required for Angiogenic Function of Bone Marrow-Derived Progenitor Cells: Role in Therapeutic Revascularization

Contact Info

Product

Resources

About