The role of thrombospondins in wound healing, ischemia, and the foreign body reaction.
Ontology highlight
ABSTRACT:
SUBMITTER: Kyriakides TR
PROVIDER: S-EPMC2778594 | biostudies-other | 2009 Dec
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of macrophages in the development of FBR. This study profiles gene expression of in vitro fibrinogen activated macrophages as well as that of freshly isolated macrophages from 3-days implants, against a background of unactivated macrophages/monocytes. Total RNA was isolated from fibrinogen activated macrophages, FBR macrophages and macrophages from blood (control). Samples were processed in triplicate on Rat Genome 230 2.0 Array GeneChips, adding up to 9 arrays in total. Microarray processing was performed at DNAVision (Charleroi, Belgium). The RMA comparisons between macrophases are linked below.
2013-01-23 | E-GEOD-21682 | biostudies-arrayexpress
Project description:Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of macrophages in the development of FBR. This study profiles gene expression of in vitro fibrinogen activated macrophages as well as that of freshly isolated macrophages from 3-days implants, against a background of unactivated macrophages/monocytes.
2013-01-23 | GSE21682 | GEO
Project description:IntroductionEpoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice.MethodsIschemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-α, TGF-β, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1α were evaluated immunohistochemically in wounds on day 3, 6, and 9.ResultsIschemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-α, TGF-β, SDF-1α, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-β, and SDF-1α expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone.ConclusionIn summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia.
| S-EPMC6335021 | biostudies-literature
Project description:Thrombospondins (TSPs) represent extracellular matrix (ECM) proteins belonging to the TSP family that comprises five members. All TSPs have a complex multidomain structure that permits the interaction with various partners including other ECM proteins, cytokines, receptors, growth factors, etc. Among TSPs, TSP1, TSP2, and TSP4 are the most studied and functionally tested. TSP1 possesses anti-angiogenic activity and is able to activate transforming growth factor (TGF)-?, a potent profibrotic and anti-inflammatory factor. Both TSP2 and TSP4 are implicated in the control of ECM composition in hypertrophic hearts. TSP1, TSP2, and TSP4 also influence cardiac remodeling by affecting collagen production, activity of matrix metalloproteinases and TGF-? signaling, myofibroblast differentiation, cardiomyocyte apoptosis, and stretch-mediated enhancement of myocardial contraction. The development and evaluation of TSP-deficient animal models provided an option to assess the contribution of TSPs to cardiovascular pathology such as (myocardial infarction) MI, cardiac hypertrophy, heart failure, atherosclerosis, and aortic valve stenosis. Targeting of TSPs has a significant therapeutic value for treatment of cardiovascular disease. The activation of cardiac TSP signaling in stress and pressure overload may be therefore beneficial.
| S-EPMC5536028 | biostudies-literature
Project description:The application of dexamethasone releasing poly (lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly vinyl alcohol (PVA) hydrogel coatings have been successfully used in the suppression of the foreign body response (FBR) to implantable glucose sensors. In the current study, dexamethasone-loaded PLGA microspheres were prepared by blending two types of PLGA polymers (RG503H and DLG7E with MW of ca. 25 kDa and 113 kDa, respectively) to achieve long-term (6 months) inhibition of the FBR. The microsphere composition was optimized according to the in vitro drug release profiles. Microspheres with DLG7E/RG503H/dexamethasone = 70/13.3/16.7 wt% composition, when embedded in a PVA hydrogel, provided a continuous drug release for 6 months. By combining the aforementioned microspheres with microspheres composed solely of the DLG7E polymer within a similar PVA hydrogel realized an even longer (>7 months) in vitro drug release. A heat map was constructed to depict the daily in vitro drug released and elucidate possible lag phases that could affect the pharmacodynamic response. These drug-loaded implant coatings were investigated in vivo (rat model) and showed inhibition of the foreign body response for 6 months. These results suggest that the minimum effective daily dose to counter chronic inflammation is ca. 0.1 μg per mg of coating surrounding a 0.5 × 0.5 × 5 mm silicon implant (dummy sensor). Accordingly, these drug-eluting composite coatings can ensure long-term inflammation control for miniaturized implantable devices.
| S-EPMC8184021 | biostudies-literature
Project description:Skin wound closure occurs when keratinocytes migrate from the edge of the wound and re-epithelialize the epidermis. Their migration takes place primarily before any vascularization is established, that is, under hypoxia, but relatively little is known regarding the factors that stimulate this migration. Hypoxia and an acidic environment are well-established stimuli for cancer cell migration. The carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. On this basis, we explored the possible role of CAs in tissue regeneration using mouse skin wound models. We show that the expression of mRNAs encoding CA isoforms IV and IX are increased (~25 × and 4 ×, respectively) during the wound hypoxic period (days 2-5) and that cells expressing CAs form a band-like structure beneath the migrating epidermis. RNA-Seq analysis suggested that the CA IV-specific signal in the wound is mainly derived from neutrophils. Due to the high level of induction of CA IV in the wound, we treated skin wounds locally with recombinant human CA IV enzyme. Recombinant CA IV significantly accelerated wound re-epithelialization. Thus, CA IV could contribute to wound healing by providing an acidic environment in which the migrating epidermis and neutrophils can survive and may offer novel opportunities to accelerate wound healing under compromised conditions.
| S-EPMC5454449 | biostudies-literature
Project description:Transcription profiling by array of wounded Nematostella juvenile polyps compared against uninjured animals and animals exposed to the MAPK inhibitor U0126
2014-03-10 | E-MTAB-2341 | biostudies-arrayexpress
Project description:PAKs are serine/threonine kinases that regulate cytoskeletal dynamics and cell migration. PAK1 is activated by binding to the small EF hand protein, CIB1, or to the Rho GTPases Rac1 or Cdc42. The role of PAK1 in angiogenesis was established based only on in vitro studies and its role in angiogenesis in vivo has never been examined. Here we tested the hypothesis that PAK1 is an essential regulator of ischemic neovascularization (arteriogenesis and angiogenesis) and wound healing using a global PAK1 knockout mouse. Neovascularization was assessed using unilateral hindlimb ischemia. We found that plantar perfusion, limb use and appearance were not significantly different between 6-8 week old PAK1-/- and PAK1+/+ mice throughout the 21-day period following hindlimb ischemia; however a slightly delayed healing was observed in 16 week old PAK1-/- mice. In addition, the wound healing rate, as assessed with an ear punch assay, was unchanged in PAK1-/- mice. Surprisingly, however, we observed a notable increase in PAK2 expression and phosphorylation in ischemic gastrocnemius tissue from PAK1-/- but not PAK1+/+ mice. Furthermore, we observed higher levels of activated ERK2, but not AKT, in ischemic and non-ischemic muscle of PAK1-/- mice upon hindlimb ischemic injury. A group I PAK inhibitor, IPA3, significantly inhibited endothelial cell sprouting from aortic rings in both PAK1-/- and PAK1+/+ mice, implying that PAK2 is a potential contributor to this process. Taken together, our data indicate that while PAK1 has the potential to contribute to neovascularization and wound healing, PAK2 may functionally compensate when PAK1 is deficient.
| S-EPMC4224450 | biostudies-literature
Project description:The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed.
| S-EPMC5555286 | biostudies-other
Project description:Electrospun materials have been widely explored for biomedical applications because of their advantageous characteristics, i.e., tridimensional nanofibrous structure with high surface-to-volume ratio, high porosity, and pore interconnectivity. Furthermore, considering the similarities between the nanofiber networks and the extracellular matrix (ECM), as well as the accepted role of changes in ECM for hernia repair, electrospun polymer fiber assemblies have emerged as potential materials for incisional hernia repair. In this work, we describe the application of electrospun non-absorbable mats based on poly(ethylene terephthalate) (PET) in the repair of abdominal defects, comparing the performance of these meshes with that of a commercial polypropylene mesh and a multifilament PET mesh. PET and PET/chitosan electrospun meshes revealed good performance during incisional hernia surgery, post-operative period, and no evidence of intestinal adhesion was found. The electrospun meshes were flexible with high suture retention, showing tensile strengths of 3 MPa and breaking strains of 8-33%. Nevertheless, a significant foreign body reaction (FBR) was observed in animals treated with the nanofibrous materials. Animals implanted with PET and PET/chitosan electrospun meshes (fiber diameter of 0.71 ± 0.28 µm and 3.01 ± 0.72 µm, respectively) showed, respectively, foreign body granuloma formation, averaging 4.2-fold and 7.4-fold greater than the control commercial mesh group (Marlex). Many foreign body giant cells (FBGC) involving nanofiber pieces were also found in the PET and PET/chitosan groups (11.9 and 19.3 times more FBGC than control, respectively). In contrast, no important FBR was observed for PET microfibers (fiber diameter = 18.9 ± 0.21 µm). Therefore, we suggest that the reduced dimension and the high surface-to-volume ratio of the electrospun fibers caused the FBR reaction, pointing out the need for further studies to elucidate the mechanisms underlying interactions between cells/tissues and nanofibrous materials in order to gain a better understanding of the implantation risks associated with nanostructured biomaterials.
| S-EPMC3989343 | biostudies-literature