scholarly journals Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling

2021 ◽  
Vol 22 (16) ◽  
pp. 8992
Author(s):  
Islamy Rahma Hutami ◽  
Takashi Izawa ◽  
Tsendsuren Khurel-Ochir ◽  
Takuma Sakamaki ◽  
Akihiko Iwasa ◽  
...  
Keyword(s):  
Wound Healing ◽  
Macrophage Activation ◽  
Important Determinant ◽  
Hypoxia Inducible Factor ◽  
Biological Regulation ◽  
Wound Site ◽  
Hypoxic Conditions ◽  
Inflammatory Conditions ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subsequently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)-1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF-1α regulates sphingosine 1-phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF-1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF-1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of monocytes/macrophages in response to circulating HIF-1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing.

Hyperferritinaemia: An Iron Sword of Autoimmunity

2019 ◽  
Vol 25 (27) ◽  
pp. 2909-2918 ◽  
Author(s):  
Joanna Giemza-Stokłosa ◽  
Md. Asiful Islam ◽  
Przemysław J. Kotyla
Keyword(s):  
Immune Response ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Catastrophic Antiphospholipid Syndrome ◽  
Inflammatory Conditions ◽  
Phase Reactant ◽  
Signalling Molecule ◽  
Cytokine Synthesis

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting

2020 ◽  
Vol 26 (36) ◽  
pp. 4551-4568
Author(s):  
Mohammad Kashif Iqubal ◽  
Sadaf Saleem ◽  
Ashif Iqubal ◽  
Aiswarya Chaudhuri ◽  
Faheem Hyder Pottoo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Wound Healing ◽  
Photodynamic Therapy ◽  
Growth Factors ◽  
Combination Therapy ◽  
Healing Process ◽  
Wound Healing Process ◽  
Wound Site ◽  
Synthetic Drugs ◽  
Treatment Paradigm

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

A bioglass sustained-release scaffold with ECM-like structure for enhanced diabetic wound healing

Nanomedicine ◽  
2020 ◽  
Vol 15 (23) ◽  
pp. 2241-2253
Author(s):  
Pengju Zhang ◽  
Yuqi Jiang ◽  
Dan Liu ◽  
Yan Liu ◽  
Qinfei Ke ◽  
...  
Keyword(s):  
Wound Healing ◽  
Therapeutic Option ◽  
Effective Strategy ◽  
Diabetic Wound ◽  
Nano Structure ◽  
Wound Site ◽  
Diabetic Wound Healing ◽  
Coaxial Fibers ◽  
Diabetic Wounds ◽  
Endothelial Cell Adhesion

Aim: To develop an effective strategy for increasing angiogenesis at diabetic wound sites and thereby accelerating wound healing. Materials & methods: A micropatterned nanofibrous scaffold with bioglass nanoparticles encapsulated inside coaxial fibers was prepared by electrospinning. Results: Si ions could be released in a sustained manner from the scaffolds. The hierarchical micro-/nano-structure of the scaffold was found to act as a temporary extracellular matrix to promote endothelial cell adhesion and growth. The scaffold greatly improved angiogenesis and collagen deposition at the wound site, which shortened the healing period of diabetic wounds. Conclusion: This study provides a promising therapeutic option for chronic diabetic wounds with improved angiogenesis.

scholarly journals A small molecule HIF-1α stabilizer that accelerates diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Von Hippel Lindau ◽  
Design And Synthesis

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.

scholarly journals Mice Deficient in Sphingosine Kinase 1 Are Rendered Lymphopenic by FTY720

2004 ◽  
Vol 279 (50) ◽  
pp. 52487-52492 ◽  
Author(s):  
Maria L. Allende ◽  
Teiji Sasaki ◽  
Hiromichi Kawai ◽  
Ana Olivera ◽  
Yide Mi ◽  
...  
Keyword(s):  
Vascular Development ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Cellular Functions ◽  
Lymphocyte Trafficking ◽  
Signaling Molecule ◽  
Physiological Functions ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
S1p Receptor

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1.Sphk1null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in mostSphk1-/-tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from theSphk1-/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs ofSphk1-/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in theSphk1null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with theseSphk1null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

scholarly journals Sphingosine 1-Phosphate (S1P) Receptor Subtypes S1P1and S1P3, Respectively, Regulate Lymphocyte Recirculation and Heart Rate

2004 ◽  
Vol 279 (14) ◽  
pp. 13839-13848 ◽  
Author(s):  
M. Germana Sanna ◽  
Jiayu Liao ◽  
Euijung Jo ◽  
Christopher Alfonso ◽  
Min-Young Ahn ◽  
...  
Keyword(s):  
Heart Rate ◽  
Receptor Subtypes ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Lymphocyte Recirculation

Impaired wound healing in embryonic and adult mice lacking vimentin

2000 ◽  
Vol 113 (13) ◽  
pp. 2455-2462 ◽  
Author(s):  
B. Eckes ◽  
E. Colucci-Guyon ◽  
H. Smola ◽  
S. Nodder ◽  
C. Babinet ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wild Type ◽  
Impaired Wound Healing ◽  
Wound Site ◽  
Adult Mice ◽  
Tractional Forces ◽  
Filament Network ◽  
Vimentin Intermediate Filament

It is generally assumed that the vimentin intermediate filament network present in most mesenchymally-derived cells is in part responsible for the strength and integrity of these cells, and necessary for any tissue movements that require the generation of significant tractional forces. Surprisingly, we have shown that transgenic KO mice deficient for vimentin are apparently able to undergo embryonic development absolutely normally and go onto develop into adulthood and breed without showing any obvious phenotype. However, fibroblasts derived from these mice are mechanically weak and severely disabled in their capacity to migrate and to contract a 3-D collagen network. To assess whether these functions are necessary for more challenging tissue movements such as those driving in vivo tissue repair processes, we have analysed wound healing ability in wild-type versus vimentin-deficient embryos and adult mice. Wounds in vimentin-deficient adult animals showed delayed migration of fibroblasts into the wound site and subsequently retarded contraction that correlated with a delayed appearance of myofibroblasts at the wound site. Wounds made to vimentin-deficient embryos also failed to heal during the 24 hour culture period it takes for wild-type embryos to fully heal an equivalent wound. By DiI marking the wound mesenchyme and following its fate during the healing process we showed that this impaired healing is almost entirely due to a failure of mesenchymal contraction at the embryonic wound site. These observations reveal an in vivo phenotype for the vimentin-deficient mouse, and challenge the dogma that key morphogenetic events occurring during development require generation of significant tractional forces by mesenchymal cells.

Analysis of hypoxia-associated dendritic cells in colitic mice and effects of probiotics on IL-10 production in inflammatory dendritic-cells under hypoxia

2019 ◽  
Vol 10 (7) ◽  
pp. 801-810
Author(s):  
T. Ogita ◽  
J. Miyamoto ◽  
Y. Hirabayashi ◽  
M. Rossi ◽  
G. Mazzarella ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Hypoxia Inducible Factor ◽  
Flow Cytometric Analysis ◽  
Bifidobacterium Bifidum ◽  
Sodium Sulphate ◽  
Mesenteric Lymph Nodes ◽  
Cellular Mechanisms ◽  
Hypoxic Conditions ◽  
Anti Inflammatory

The aim of this study was to analyse hypoxia-associated dendritic cells (DCs) in colitic mice and the effects of probiotics on interleukin (IL)-10 production in inflammatory DCs under hypoxic conditions. Extensive hypoxia was observed in the colonic mucosa of dextran sodium sulphate-induced colitic mice. Flow cytometric analysis demonstrated that hypoxia-inducible factor-1α+ DCs in colonic lamina propria (CLP) lymphocytes and mesenteric lymph nodes (MLN) were more abundant in colitic mice than those in controls. Among three subsets of DCs, i.e. plasmacytoid DCs, conventional DCs (cDCs), and monocyte-derived DCs (mDCs), cDCs and mDCs were more abundant in CLP of colitic mice. Bone marrow-derived Flt-3L-induced DCs (Flt-DCs) but not bone marrow-derived GM-CSF-induced DCs (GM-DCs), incubated with 1% O2 exhibited an inflammatory phenotype, with higher CD86, IL-6, and tumour necrosis factor-α expression, and lower IL-10 levels than those in Flt-DCs incubated with 21% O2. The hypoxia-induced decrease in IL-10 expression in Flt-DCs was restored by Bifidobacterium bifidum JCM 1255T promoted IL-10 expression through the p38 pathway under normoxic conditions. The anti-inflammatory effects of B. bifidum JCM 1255T in Flt-DCs were mediated through different cellular mechanisms under hypoxic and normoxic conditions. B. bifidum JCM 1255T could be used therapeutically for its anti-inflammatory effects.

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