Yvonne Marcoux
University of Alberta
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Featured researches published by Yvonne Marcoux.
Molecular and Cellular Biochemistry | 2005
Grzegorz Sawicki; Yvonne Marcoux; Kourosh Sarkhosh; Edward E. Tredget; Aziz Ghahary
Disruption of epidermal-mesenchymal communication due to a delay in epithelialization, increases the frequency of developing fibrotic conditions in skin. As matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) are two key enzymes involved in wound healing and tissue remodeling, here we examined the efficacy of keratinocyte-fibroblast interaction on modulation of these enzymes and their inhibitors. The conditioned media derived from keratinocytes and fibroblasts grown in upper and lower chambers of a co-culture system, respectively, were analyzed for MMP-2 and -9. Keratinocyte or fibroblast conditioned medium (FCM) was used as a control. Gelatinolytic activity analyzed by zymography showed that keratinocytes mainly express MMP-9 and to a lesser extent MMP-2; while fibroblasts express only MMP-2. In a co-culture system, the activities of both MMP-2 and MMP-9 markedly increased in conditioned media collected from bottom chambers. These findings were consistent with the level of MMP-2 and MMP-9 measured by Western blot. Using the same experimental setting, the levels of tissue inhibitors of MMPs (TIMPs) secreted by keratinocytes and fibroblasts grown in the same co-culture system were also evaluated. Western blot showed that fibroblasts secrete only TIMP-1 and TIMP-2 whose levels were increased by co-culturing fibroblasts with keratinocytes. In contrary the level of TIMP-3, which was mainly expressed by keratinocytes, increased by co-culturing these cells with fibroblasts. In conclusion, interaction of fibroblast-keratinocyte modulates the levels of MMP-2 and -9 and their inhibitors produced by these cells and this interaction may be critical for a better healing quality at a late stage of the wound healing process. (Mol Cell Biochem 269: 209–216, 2005)
Wound Repair and Regeneration | 2011
Jie Ding; Keijiro Hori; Rainny Zhang; Yvonne Marcoux; Dariush Honardoust; Heather A. Shankowsky; Edward E. Tredget
Recent data support the involvement of stromal cell‐derived factor 1 (SDF‐1) in the homing of bone marrow‐derived stem cells to wound sites during skeletal, myocardial, vascular, lung, and skin wound repair as well as some fibrotic disorders via its receptor CXCR4. In this study, the role of SDF‐1/CXCR4 signaling in the formation of hypertrophic scar (HTS) following burn injury and after treatment with systemic interferon α2b (IFNα2b) is investigated. Studies show SDF‐1/CXCR4 signaling was up‐regulated in burn patients, including SDF‐1 level in HTS tissue and serum as well as CD14+CXCR4+ cells in the peripheral blood mononuclear cells. In vitro, dermal fibroblasts constitutively expressed SDF‐1 and deep dermal fibroblasts expressed more SDF‐1 than superficial fibroblasts. Lipopolysaccharide increased SDF‐1 gene expression in fibroblasts. Also, recombinant SDF‐1 and lipopolysaccharide stimulated fibroblast‐conditioned medium up‐regulated peripheral blood mononuclear cell mobility. In the burn patients with HTS who received subcutaneous IFNα2b treatment, increased SDF‐1/CXCR4 signaling was found prior to treatment which was down‐regulated after IFNα2b administration, coincident with enhanced remodeling of their HTS. Our results suggest that SDF‐1/CXCR4 signaling is involved in the development of HTS by promoting migration of activated CD14+CXCR4+ cells from the bloodstream to wound sites, where they may differentiate into fibrocyte and myofibroblasts and contribute to the development of HTS.
Journal of Burn Care & Research | 2012
Dariush Honardoust; Mathew Varkey; Yvonne Marcoux; Heather A. Shankowsky; Edward E. Tredget
Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-&bgr;1 and small leucine-rich proteoglycans (SLRPs) with fibroblast subtype and function may influence the development of HTS. The aim of this study was to characterize the expression and localization of factors that regulate wound healing including SLRPs, TGF-&bgr;1, and TGF-&bgr;3 in an experimental human SW and deep wound (DW) scar model including fibroblasts from superficial and deep layers of normal dermis. A 6-cm horizontal dermal scratch experimental wound was created, which consisted of progressively deeper wounds that were superficial at one end (0–0.75 mm deep) and deep (0.75–3 mm deep) at the other end, located on the anterior thigh of an adult male. Immunofluorescence staining, immunoblotting, reverse transcription polymerase chain reaction, and flow cytometry were performed to analyze the cellular and molecular differences between the SW scar and DW scar as well as fibroblasts isolated from superficial layer (L1) and deep layer (L5) of normal dermis. Comparing SWs and L1 fibroblasts, the expression of decorin, fibromodulin, and TGF-&bgr;3 was considerably lower than in DWs and L5 fibroblasts; however, TGF-&bgr;1 was higher in the deeper dermal wounds. When compared with L1 fibroblasts, L5 fibroblasts had lower Thy-1 immunoreactivity and significantly higher expression of TGF-&bgr; receptor type II. Decreased antifibrotic molecules in matrix of deep dermis of the skin and the unique features of the associated fibroblasts including an increased sensitivity to TGF-&bgr;1 stimulation contribute to the development of HTS after injuries involving the deep dermis.
Cell Transplantation | 2002
Wilma L. Suarez-Pinzon; Yvonne Marcoux; Aziz Ghahary; Alex Rabinovitch
Nonobese diabetic (NOD) mice develop diabetes and destroy syngeneic islet grafts through an autoimmune response. Because transforming growth factor (TGF)-β1 downregulates immune responses, we tested whether overexpression of TGF-β1 by gene transfection of NOD mouse islets could protect β-cells in islet grafts from autoimmune destruction. NOD mouse islet cells were transfected with an adenoviral DNA expression vector encoding porcine latent TGF-β1 (Ad TGF- β1) or the adenoviral vector alone (control Ad vector). The frequency of total islet cells expressing TGF-1 protein was increased from 12±1% in control Ad vector-transfected cells to 89 ± 4% in Ad TGF-β1-transfected islet cells, and the frequency of β-cells that expressed TGF-β1 was increased from 12 ± 1% to 60 ± 7%. Also, secretion of TGF-β1 was significantly increased in islets that overexpressed TGF-β1. Ad TGF-β1-transfected NOD mouse islets that overexpressed TGF-β1 prevented diabetes recurrence after transplantation into diabetic NOD mice for a median of 22 days compared with only 7 days for control Ad vector-transfected islets (p = 0.001). Immunohistochemical examination of the islet grafts revealed significantly more TGF-β1+ cells and insulin+ cells and significantly fewer CD45+ leukocytes in Ad TGF-β1-transfected islet grafts. Also, islet β-cell apoptosis was significantly decreased whereas apoptosis of graft-infiltrating leukocytes was significantly increased in Ad TGF-β1-transfected islet grafts. These observations demonstrate that overexpression of TGF-β1, by gene transfection of NOD mouse islets, protects islet β-cells from apoptosis and autoimmune destruction and delays diabetes recurrence after islet transplantation.
Journal of Cellular Biochemistry | 2001
Aziz Ghahary; Yvonne Marcoux; Feridoun Karimi-Busheri; Edward E. Tredget
Extensive skin loss from a variety of conditions such as severe thermal injury is associated with significant functional morbidity and mortality. In recent years, the healing quality has been improved for patients who suffer burns due in part to the usage of skin replacement mainly prepared from multi‐layered sheets of cultured keratinocytes. Although it is known that keratinocytes are a rich source of wound healing promoting factors such as transforming growth factor‐β1 (TGF‐β1), it is not clear whether differentiated keratinocytes in a multi‐layer form release this multi‐functional growth factor and has any functional influence on dermal fibroblasts. This study examined the hypothesis that keratinocytes in mono‐ and multi‐layer forms express different levels of TGF‐β1. To address this hypothesis, keratinocytes were grown in serum free medium (KSFM) supplemented with bovine pituitary extract (50 μg/ml) and EGF (5 μg/ml). When cells reached confluency, conditioned medium was removed and replaced with 50% KSFM with no additives and 50% DMEM without serum and cells were allowed to form multi‐layers and differentiate. The conditioned medium was then collected every 48 h up to 24 days and the level of TGF‐β1 and the efficacy of a keratinocyte released fibroblast mitogenic factor were evaluated by ELISA and 3H‐thymidine incorporation, respectively. Northern analysis was also employed to evaluate the expression of TGF‐β1, involucrin, TIMP‐1, and 18 S ribosomal RNA in keratinocytes at different times of the onset of differentiation. The microscopic morphology of keratinocytes at different times of induction of cell differentiation showed detachments (nodules) of many regions of keratinocyte sheet from culture substratum within 1–2 weeks. The numbers and sizes of these nodules were increased as the process of keratinocyte differentiation proceed. The results of TGF‐β1 evaluation revealed that mono‐layers of cultured keratinocytes which were round, attached, and proliferating in KSFM + BPE and EGF containing medium released a significantly higher level of TGF‐β1 (196 ± 58 pg /ml) relative to those grown in multi‐layer forms (28 ± 7.8 pg/ml). A longitudinal experiment was then conducted and the results showed that cells on the onset of differentiation released even greater level of TGF‐β1 (388 ± 53 pg/ml) relative to those grown in KSFM + BPE and EGF. This finding was consistent with the expression of TGF‐β1 mRNA evaluated in keratinocytes grown in test medium for various duration. In general, the level of TGF‐β1 protein and mRNA gradually reduced to its lowest level within 12 days of growing cells in our test medium. When aliquots of the collected keratinocyte conditioned medium were added to dermal fibroblasts, the level of 3H‐thymidine incorporation increased only in those cells receiving aliquots of conditioned medium containing high levels of TGF‐β1. When involucrin was used as a differentiation marker for keratinocytes at different time points, the highest level of involucrin mRNA expression was found at the later stage of cell differentiation. In conclusion, high involucrin expressing differentiated keratinocytes seem to be quiescent in releasing both TGF‐β1 and a fibroblast mitogenic factor. J. Cell. Biochem. 83: 239–248, 2001.
Journal of Cellular Biochemistry | 2002
Feridoun Karimi-Busheri; Yvonne Marcoux; Edward E. Tredget; Liang Li; Jing Zheng; Mina Ghoreishi; Michael Weinfeld; Aziz Ghahary
Annexin II is a multifunctional calcium‐dependent phospholipid binding protein whose presence in epidermis has previously been reported. However, like other members of annexin family, annexin II has been regarded as either an intracellular protein or associated with the cellular membrane. Here, we report the presence of a releasable annexin II and p11, two monomers of annexin II tetramer, in keratinocyte‐conditioned medium (KCM). Proteins present in KCM were fractionated on a gel filtration column and following further evaluation, a releasable protein with apparent MW of 36 kDa was identified. Further characterization identified this protein as the p36 monomer of annexin II tetramer. The phospho‐tyrosine antibody did not visualize this protein as the phosphorylated form of p36. Several experiments were conducted to examine whether this protein is soluble or associated with keratinocyte cell membranes in the conditioned medium. A centrifugation of conditioned medium was not able to bring this protein down into the pellet. Surprisingly, the results of Western analysis identified p36 and p11, two monomers of the annexin II tetramer, in conditioned medium derived from either keratinocytes cultured alone or keratinocytes co‐cultured with fibroblasts. In contrast to the keratinocyte‐conditioned medium in which annexin II was easily detectable, both monomers were barely detectable in conditioned medium collected from dermal fibroblasts. This finding was in contrast to the cell lysates in which p36 was detectable in both keratinocytes and fibroblasts. However, the amount of this protein was markedly higher in keratinocyte lysate relative to that of dermal fibroblasts. Conditioned medium derived from keratinocyte established from adult showed a higher level of annexin II compared to that of keratinocytes established from newborn babies. The expression of p11 seems to increase with differentiation of keratinocytes derived from either adult or newborn skin samples. When the site of annexin synthesis in human skin was examined by immunohistochemical staining, the antibody for p36 localized the annexin to the keratinocyte cell members in the basal and suprabasal keratinocytes. In conclusion, Western blot detection of both p36 and p11 in conditioned medium from skin cells revealed that human keratinocytes, but not fibroblasts, express a releasable monomer form of annexin II which is regulated by differentiation status of keratinocytes. This finding is consistent with the localization of annexin II detected by immunohistochemical staining. J. Cell. Biochem. 86: 737–747, 2002.
Wound Repair and Regeneration | 2012
Keijiro Hori; Jie Ding; Yvonne Marcoux; Takashi Iwashina; Hiroyuki Sakurai; Edward E. Tredget
Transforming growth factor‐β inducible early gene (TIEG) is induced by transforming growth factor‐β (TGF‐β) and acts as the primary response gene in the TGF‐β/Smad pathway. TGF‐β is a multifunctional growth factor that affects dermal wound healing; however, the mechanism of how TGF‐β affects wound healing is still not well understood because of the complexity of its function and signaling pathways. We hypothesize that TIEG may play a role in dermal wound healing, with involvement in wound closure, contraction, and reepithelialization. In this study, we have shown that TIEG1 knockout (TIEG1–/–) mice have a delay in wound closure related to an impairment in wound contraction, granulation tissue formation, collagen synthesis, and reepithelialization. We also found that Smad7 was increased in the wounds and appeared to play a role in this wound healing model in TIEG1–/– mice.
Molecular and Cellular Biochemistry | 2004
Eugene Lam; Edward E. Tredget; Yvonne Marcoux; Yunyuan Li; Aziz Ghahary
A delicate balance between synthesis and degradation of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is an essential feature of tissue remodeling. We have recently demonstrated that keratinocyte releasable stratifin, also known as 14-3-3 σ protein, plays a critical role in modulating collagenase (MMP-1) mRNA expression in human dermal fibroblasts. In this study, we further characterized the collagenase stimulatory effect of stratifin in dermal fibroblasts and evaluated its effect in the presence and absence of insulin. Our data indicate that stratifin increases the expression of collagenase mRNA more than 20-fold in dermal fibroblasts, grown in either Dulbeccos modified Eagles medium (DMEM) plus 2% or 10% fetal bovine serum (FBS). Collagenase stimulatory effect of stratifin was completely blocked, when fibroblasts were cultured in test medium consisting of 50% keratinocyte serum-free medium (KSFM) and 50% DMEM. The collagenase suppressive effect of test medium was directly proportional to the volume of KSFM used. As this medium contained insulin, we then evaluated the collagenase stimulatory effect of stratifin in dermal fibroblasts in the presence and absence of insulin. The results revealed that stratifin significantly increased the expression of collagenase mRNA/18S (*p < 0.05, n= 3) ratio, while insulin significantly decreased the expression of collagenase mRNA/18S (*p < 0.05, n= 3) ratio. The insulin inhibitory effect on collagenase mRNA expression was time and dose dependent. The maximal inhibitory effect of insulin was seen at 36 h post treatment. In conclusion, stratifin stimulates the expression of collagenase mRNA expression in dermal fibroblasts and this effect is suppressed by insulin treatment (Mol Cell Biochem 266: 167–174, 2004)
Journal of Investigative Dermatology | 2004
Aziz Ghahary; Feridoun Karimi-Busheri; Yvonne Marcoux; Yunyaun Li; Edward E. Tredget; Liang Li; Jing Zheng; Ali Karami; Bernd O. Keller; Michael Weinfeld; Ruhangiz T. Kilani
Journal of Investigative Dermatology | 2005
Aziz Ghahary; Yvonne Marcoux; Feridoun Karimi-Busheri; Yunyaun Li; Edward E. Tredget; Ruhangiz T. Kilani; Eugene Lam; Michael Weinfeld