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Fibrosis And Additional And Wound Healing And Animal Models

Maria Pina Dore, Giovanni Mario Pes, Alessandra Errigo, Alessandra Manca, Giuseppe Realdi
Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H...
December 12, 2018: Experimental Biology and Medicine
Christine Linard, Michel Brachet, Carine Strup-Perrot, Bruno L'homme, Elodie Busson, Claire Squiban, Valerie Holler, Michel Bonneau, Jean-Jacques Lataillade, Eric Bey, Marc Benderitter
Cutaneous radiation syndrome has severe long-term health consequences. Because it causes an unpredictable course of inflammatory waves, conventional surgical treatment is ineffective and often leads to a fibronecrotic process. Data about the long-term stability of healed wounds, with neither inflammation nor resumption of fibrosis, are lacking. In this study, we investigated the effect of injections of local autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs), combined with plastic surgery for skin necrosis, in a large-animal model...
August 2018: Stem Cells Translational Medicine
Manreet Padwal, Genyang Cheng, Limin Liu, Felix Boivin, Azim S Gangji, Kenneth S Brimble, Darren Bridgewater, Peter J Margetts
The wingless-type mouse mammary tumor virus integration site family (WNT) signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor-β (TGF-β)-mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis...
June 1, 2018: American Journal of Physiology. Renal Physiology
Thiagarajan Venkataraman, Christopher M Coleman, Matthew B Frieman
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage...
June 15, 2017: Journal of Virology
Lu Jiang, Pingping Fang, James L Weemhoff, Udayan Apte, Michele T Pritchard
Autosomal recessive polycystic kidney disease (ARPKD) is a severe monogenic disorder that occurs due to mutations in the PKHD1 gene. Congenital hepatic fibrosis (CHF) associated with ARPKD is characterized by the presence of hepatic cysts derived from dilated bile ducts and a robust, pericystic fibrosis. Cyst growth, due to cyst wall epithelial cell hyperproliferation and fluid secretion, is thought to be the driving force behind disease progression. Liver fibrosis is a wound healing response in which collagen accumulates in the liver due to an imbalance between extracellular matrix synthesis and degradation...
2016: BioMed Research International
Shailesh Agarwal, Shawn Loder, David Cholok, Joshua Peterson, John Li, David Fireman, Christopher Breuler, Hsiao Sung Hsieh, Kavitha Ranganathan, Charles Hwang, James Drake, Shuli Li, Charles K Chan, Michael T Longaker, Benjamin Levi
Endothelial-to-mesenchymal transition (EndMT) has been implicated in a variety of aberrant wound healing conditions. However, unambiguous evidence of EndMT has been elusive due to limitations of in vitro experimental designs and animal models. In vitro experiments cannot account for the myriad ligands and cells which regulate differentiation, and in vivo tissue injury models may induce lineage-independent endothelial marker expression in mesenchymal cells. By using an inducible Cre model to mark mesenchymal cells (Scx-creERT/tdTomato + ) prior to injury, we demonstrate that musculoskeletal injury induces expression of CD31, VeCadherin, or Tie2 in mesenchymal cells...
September 12, 2016: Scientific Reports
Jung U Shin, Seo Hyeong Kim, Hyeran Kim, Ji Yeon Noh, Shan Jin, Chang Ook Park, Won Jai Lee, Dong Won Lee, Ju Hee Lee, Kwang Hoon Lee
Recently, thymic stromal lymphopoietin (TSLP), which is well studied in allergic diseases, has been reported in fibrotic diseases, including idiopathic pulmonary fibrosis and atopic dermatitis fibrosis. However, the role of TSLP in keloid is obscure. In this study, we assessed the expression of TSLP in keloid tissue and investigated the possible role of TSLP in keloid pathogenesis. We observed that TSLP expression was increased in keloid tissue compared to normal tissue. Furthermore, TSLP treatment induced increased collagen I and collagen III expression in fibroblasts via transforming growth factor-?; however, there was higher expression in keloid fibroblasts compared to normal fibroblasts...
February 2016: Journal of Investigative Dermatology
Andre A M Torricelli, Abirami Santhanam, Jiahui Wu, Vivek Singh, Steven E Wilson
The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts...
January 2016: Experimental Eye Research
Di Liang, Yan Wang, Zhonghui Zhu, Gengxia Yang, Guoliang An, Xiaoli Li, Piye Niu, Li Chen, Lin Tian
OBJECTIVE: To investigate the anti-fibrotic effects and possible mechanisms of bone morphogenetic protein-7 (BMP-7) on silica induced fibrosis in RLE-6TN cells, and compare the preventive treatment of experimental silicosis with BMP-7 with therapeutic treatment of silicosis in vitro models. METHODS: RLE-6TN cells were incubated with the supernatant of RAW264.7, treated by 50 μg/mL silica in either presence or absence of BMP-7 in different phases. Morphological changes and the cellular wound-healing assays were used to evaluate the process of EMT...
January 5, 2016: Chemico-biological Interactions
Hui Zhang, Qingfeng Sun, Tingyan Xu, Liang Hong, Rongquan Fu, Jinguo Wu, Jiguang Ding
Liver fibrosis is a wound-healing response to chronic liver injury that results in the accumulation of extracellular matrix proteins. It eventually leads to cirrhosis of the liver and liver failure, and it is a critical threat to the health and lives of patients with chronic liver diseases. No effective treatment is currently available. Resveratrol is a polyphenol with antioxidant, anti‑cancer and anti‑inflammatory properties. It has been reported that resveratrol prevents liver fibrosis, possibly by inhibiting NF‑κB activation...
January 2016: Molecular Medicine Reports
Ulrich Valcourt, Jonathon Carthy, Yukari Okita, Lindsay Alcaraz, Mitsuyasu Kato, Sylvie Thuault, Laurent Bartholin, Aristidis Moustakas
In recent years, the importance of the cell biological process of epithelial-mesenchymal transition (EMT) has been established via an exponentially growing number of reports. EMT has been documented during embryonic development, tissue fibrosis, and cancer progression in vitro, in animal models in vivo and in human specimens. EMT relates to many molecular and cellular alterations that occur when epithelial cells undergo a switch in differentiation that generates mesenchymal-like cells with newly acquired migratory and invasive properties...
2016: Methods in Molecular Biology
Fatih Candas, Rauf Gorur, Aptullah Haholu, Akin Yildizhan, Orhan Yucel, Hakan Ay, Ali Memis, Turgut Isitmangil
BACKGROUND: Allografts have achieved prominence for tracheal reconstruction because of their natural physiologic and anatomic structure, which preserves respiratory tract flexibility and lumen patency. The immunomodulatory effects of cryopreservation prevent tracheal allograft rejection. In addition, hyperbaric oxygen therapy (HBOT) accelerates wound healing by promoting epithelization and neovascularization. This experimental study investigated the early and late effects of HBOT on cryopreserved tracheal allografts (CTAs)...
March 2016: Annals of Thoracic Surgery
Martine Ben Amar, Min Wu, Miguel Trejo, Michael Atlan
Inflammatory fibrosis is a wound-healing reaction of the immune system in mammals against aggression. After a signalling cascade, fibroblasts and potentially myofibroblasts make a stiff collagenous tissue inside the body that modifies the original healthy tissue. We focus here on the implant-induced fibrosis that aims to encapsulate the implant with a typical fibrous tissue called the capsule. Focusing on breast capsules, we aim to understand the mechanical properties of these tissues, to test the validity of fibre models that have been established in other contexts such as arteries...
October 6, 2015: Journal of the Royal Society, Interface
William C W Chen, Brandon G Lee, Dae Woo Park, Kyobum Kim, Hunghao Chu, Kang Kim, Johnny Huard, Yadong Wang
Myocardial infarction (MI) causes myocardial necrosis, triggers chronic inflammatory responses, and leads to pathological remodeling. Controlled delivery of a combination of angiogenic and immunoregulatory proteins may be a promising therapeutic approach for MI. We investigated the bioactivity and therapeutic potential of an injectable, heparin-based coacervate co-delivering an angiogenic factor, fibroblast growth factor-2 (FGF2), and an anti-inflammatory cytokine, Interleukin-10 (IL-10) in a spatially and temporally controlled manner...
December 2015: Biomaterials
Annika Andersson-Sjöland, Jenny C Karlsson, Kristina Rydell-Törmänen
Pulmonary fibrosis is a grave diagnosis with insidious progression, generally considered as a consequence of aberrant epithelial wound healing and excessive scarring. This process is commonly modeled in animals by local bleomycin administration, resulting in peribronchial inflammation and subsequent fibrosis. We have previously described initiation and early development of distal pulmonary fibrosis following repeated subcutaneous bleomycin injections (systemic administration). The aim of this study was to identify mechanisms for the development of pulmonary fibrosis, which we hypothesize is related to endothelial stress and activation...
February 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kai Zheng, Weizhen Wu, Shunliang Yang, Lianghu Huang, Jin Chen, Chungui Gong, Zhichao Fu, Linlin Zhang, Jianming Tan
The present study aimed to observe the role of mesenchymal stem cells (MSCs) in the repair of acute skin damage caused by radiation. Rat bone marrow MSCs (BMSCs) were isolated and cultured in vitro. A rat model of radiation‑induced acute skin damage was established by irradiation of the hind legs of Sprague-Dawley rats using a linear accelerator (45 Gy). After irradiation, rats were randomly divided into two groups: BMSC group and control group. Rats in the BMSC group were treated with a tail vein injection of 2x106 BMSCs (1 ml) immediately after irradiation and a local multipoint injection of 2x106 BMSCs at the injured area two weeks later...
November 2015: Molecular Medicine Reports
Ying-Hsien Huang, Mao-Meng Tiao, Li-Tung Huang, Jiin-Haur Chuang, Kuang-Che Kuo, Ya-Ling Yang, Feng-Sheng Wang
BACKGROUND: Recent studies have shown that microRNA-29 (miR-29) is significantly decreased in liver fibrosis and that its downregulation influences the activation of hepatic stellate cells (HSCs). In addition, inhibition of the activity of histone deacetylases 4 (HDAC4) has been shown to strongly reduce HSC activation in the context of liver fibrosis. OBJECTIVES: In this study, we examined whether miR-29a was involved in the regulation of HDAC4 and modulation of the profibrogenic phenotype in HSCs...
2015: PloS One
Dikshya Bastakoty, Sarika Saraswati, Justin Cates, Ethan Lee, Lillian B Nanney, Pampee P Young
Wound healing in mammals is a fibrotic process. The mechanisms driving fibrotic (as opposed to regenerative) repair are poorly understood. Herein we report that therapeutic Wnt inhibition with topical application of small-molecule Wnt inhibitors can reduce fibrosis and promote regenerative cutaneous wound repair. In the naturally stented model of ear punch injury, we found that Wnt/β-catenin pathway is activated most notably in the dermis of the wound bed early (d 2) after injury and subsides to baseline levels by d10...
December 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Tobias Kühl, Markus Mezger, Ingrid Hausser, Rupert Handgretinger, Leena Bruckner-Tuderman, Alexander Nyström
Dystrophic epidermolysis bullosa (DEB) is an incurable skin fragility disorder caused by mutations in the COL7A1 gene, coding for the anchoring fibril protein collagen VII (C7). Life-long mechanosensitivity of skin and mucosal surfaces is associated with large body surface erosions, chronic wounds, and secondary fibrosis that severely impede functionality. Here, we present the first systematic long-term evaluation of the therapeutic potential of a mesenchymal stromal cell (MSC)-based therapy for DEB. Intradermal administration of MSCs in a DEB mouse model resulted in production and deposition of C7 at the dermal-epidermal junction, the physiological site of function...
August 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Morten A Karsdal, Tina Manon-Jensen, Federica Genovese, Jacob H Kristensen, Mette J Nielsen, Jannie Marie B Sand, Niels-Ulrik B Hansen, Anne-Christine Bay-Jensen, Cecilie L Bager, Aleksander Krag, Andy Blanchard, Henrik Krarup, Diana J Leeming, Detlef Schuppan
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated...
May 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
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