Angiogenic Growth Factors: Their Effects and Potential in Soft Tissue Wound Healing

Hom, David B.; Maisel, Robert H.

doi:10.1177/000348949210100411

Cited by 90 publications

(55 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Leptin produced in placental trophoblasts may act in concert with other placental angiogenic factors to regulate placental vascularization and transplacental exchange (51). During wound healing, leptin production may be required for supporting angiogenesis, 2 which is necessary for granulation tissue formation (52), or perhaps for additional functions including keratinogenesis (53,54) or local production of angiogenic cytokines such as vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor-␤ (9,55,56). One commonality among all of these different scenarios in which leptin is produced may be the establishment of a hypoxic environment that necessitates the appropriate underlying machinery to provide an attendant physiological adaptation response.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Activation of the Human Leptin Gene in Response to Hypoxia

Ambrosini

Nath

Sierra-Honigmann

et al. 2002

Journal of Biological Chemistry

177

109

View full text Add to dashboard Cite

In addition to having a major role in energy homeostasis, leptin is emerging as a pleiotropic cytokine with multiple physiological effector functions. The recently discovered proangiogenic activity of leptin suggested the hypothesis that its production might be regulated by hypoxia, as are other angiogenic factors. To examine this proposal, the expression of leptin protein and mRNA was measured and found to be markedly up-regulated in response to ambient or chemical hypoxia (upon exposure to desferrioxamine or cobalt chloride), an effect that requires intact RNA synthesis, suggesting a transcriptional mechanism. Transient transfection of cultured cells with deletion constructs of the leptin gene promoter linked to a reporter gene revealed a functional hypoxia response element (HRE) located at position -116 within the proximal upstream region. This putative HRE harbors a characteristic 5-RCGTG-3 core motif, a hallmark of hypoxia-sensitive genes and recognized by the hypoxia-inducible factor 1 (HIF1), which consists of a HIF1␣/HIF␤ heterodimer. Constructs harboring this -116/HRE supported reporter gene expression in response to hypoxia but not when mutated. Expression of HIF1␣ cDNA in normoxic cells mimicked hypoxia-induced reporter gene expression in cells cotransfected with the wild type leptin -116/HRE construct but not with the mutant. Gel shift assays with a 32 P-labeled leptin promoter -116/HRE probe and nuclear extracts from hypoxia-treated cells indicated binding of the HIF1␣/␤ heterodimer, which was blocked with an excess of unlabeled -116/HRE probe or a HIF1-binding probe from the erythropoietin gene enhancer. Taken together, these observations demonstrate that the leptin gene is actively engaged by hypoxia through a transcriptional pathway commonly utilized by hypoxia-sensitive genes.Physiological mechanisms that ensure an appropriate level of oxygen (O 2 ) delivery to tissues have evolved in complex multicellular organisms. Virtually all cells are capable of sensing changes in O 2 tension (pO 2 ) and respond adaptively when the O 2 demand exceeds supply, a condition referred to as hypoxia (1). Hypoxia can develop as a result of ischemia resulting from hypoperfusion, either as a pathological condition or as a transient physiological event (1). Under chronic conditions of hypoxia, typical adaptation responses generally include changes in the expression of genes encoding molecules that facilitate O 2 delivery or by activating metabolic pathways that do not require O 2 , thus maintaining energy homeostasis when O 2 availability is limited (1, 2). For example, hypobaric hypoxia leads to a classical response characterized by increased red blood cell mass formation after induction of the erythropoietin (Epo) 1 gene, whose expression is elevated markedly under these conditions (3, 4). In addition, the vasodilators nitric oxide and carbon monoxide are generated by the catalytic activity of inducible nitric oxide and heme oxygenase-1, respectively; expression of the genes encoding these enzymes is induced readil...

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional Activation of the Human Leptin Gene in Response to Hypoxia

Ambrosini

Nath

Sierra-Honigmann

et al. 2002

Journal of Biological Chemistry

177

109

View full text Add to dashboard Cite

show abstract

“…To date, several growth factors have been characterized and introduced [91][92][93][94][95][96][97][98][99]. The main important wellknown growth factors are basic and acidic Fibroblast Growth Factor (FGF), Vasculoendothelial Growth Factor (VEGF), Transforming Growth Factor beta (TGF-β), Platelet Derived Growth Factor (PDGF), bone morphogenic protein (BMP), etc.…”

Section: Healing Promotive Factorsmentioning

confidence: 99%

“…It has a role in migration and proliferation of endothelial cells and therefore can accelerate angiogenesis, short term after injury [94,96,97]. VEFG regulates and increases the migration and proliferation of endothelial cells and both the FGF and VEGF have a strong role in cell differentiation shortly after injury induction and during the initial stages of wound healing [30,[95][96][97][98][99]. PDGF is released from the alpha granules of the aggregated and activated platelets after injury and have crucial roles in regulating different stages of healing [30,91,100].…”

Section: Healing Promotive Factorsmentioning

confidence: 99%

Tendon and Ligament Tissue Engineering, Healing and Regenerative Medicine

Moshiri¹,

Oryan²

2013

J Sports Med Doping Stud 2013

102

View full text Add to dashboard Cite

Tendons transmit forces from muscle to bone and provide the joint function and ligaments transmit forces from bone to bone and provide joint stability. Tendon and ligament injuries have high incidence and management of tendon and ligament injuries is technically demanding because the healing response of these soft connective tissues is low. In addition, number of the available options to be considered as tissue replacement for large defects is low and healing of tendon and ligaments is faced to significant limitations. Among the available options, autografts are still gold standard but all the auto-allo and xenografts have their own limitations. Tissue engineering is a newer option but it is still primitive to be applicable extensively, in clinical setting. Tissue engineering could be divided into four categories including scaffolds, healing promotive factors, stem cells and gene therapy. To be able to have a good judgment regarding the management of tendon and ligament injuries, it is crucial to have a basic knowledge of tendon and ligament healing and regeneration. In this review, we discussed various types of tendon and ligament injuries and their incidence, and introduced the available and future options in managing large and massive tendon and ligament injuries. We specifically discussed the tissue engineering and it's advantageous and disadvantageous. To give a better clarification for the readers, we described different phases and cascades of tendon and ligament healing, modeling and remodeling, host-graft interaction after implantation of the graft and various types of prosthetic implants and finally provided some suggestions for the future investigations.

show abstract

“…in addition, these same growth factors activate tissue macrophages, thereby releasing FGF, TGF or PdGF. These factors again connect to endothelial tissue and stimulate angiogenesis (13,14). The final phase, known as the 'phase of repair', consists of filling up of the wound with connective tissue.…”

Section: First To Third Day: Exudative Phase (Phase Of Physiological mentioning

confidence: 99%

Keloids: Fundamental principles and prospects (Review)

Gieringer

Elliott²,

Gosepath³

et al. 2009

Mol Med Rep

View full text Add to dashboard Cite

Abstract. Wound healing is a very complex process of interactions between different cells, growth factors, blood elements and extracellular matrix. Keloids represent one of the possible complications in the fundamental process of cutaneous wound repair. despite all efforts, keloids remain a therapeutic challenge since no treatment is as yet considered 100% effective. Growth factors, discovered in the late 1970s, have been shown to influence dermal regeneration. However, the exogenous application of growth factors to chronic wounds has not proven to be effective in healing them. additionally, genetic analysis has not revealed any single gene that might cause keloids; as such, classic gene therapy is not a feasible option for the treatment of keloids. a new approach is so-called somatic gene therapy. This review provides an overview of the fundamentals of wound healing and of keloids, and presents new possibilities that may improve cutaneous wound repair.

show abstract

Angiogenic Growth Factors: Their Effects and Potential in Soft Tissue Wound Healing

Cited by 90 publications

References 30 publications

Transcriptional Activation of the Human Leptin Gene in Response to Hypoxia

Transcriptional Activation of the Human Leptin Gene in Response to Hypoxia

Tendon and Ligament Tissue Engineering, Healing and Regenerative Medicine

Keloids: Fundamental principles and prospects (Review)

Contact Info

Product

Resources

About