scholarly journals Recombinant nAG (a Salamander-Derived Protein) Decreases the Formation of Hypertrophic Scarring in the Rabbit Ear Model

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Mohammad M. Al-Qattan ◽  
Mervat M. Abd-Al Wahed ◽  
Khalid Hawary ◽  
Ahmed A. Alhumidi ◽  
Medhat K. Shier
Keyword(s):  
Human Fibroblasts ◽  
Local Injection ◽  
Collagen I ◽  
Hypertrophic Scarring ◽  
Collagen Expression ◽  
Rabbit Ear ◽  
Primary Fibroblasts ◽  
Scar Maturation ◽  
Scar Hypertrophy

nAG (newt-Anterrior Gradient) protein is the key mediator of regrowth of amputated limbs in salamanders. In a previous work in our lab, a newnAGgene (suitable for humans) was designed and cloned. The cloned vector was transfected into primary human fibroblasts. The expression ofnAGin human primary fibroblasts was found to suppress collagen expression. The current study shows that local injection of recombinant nAG reduces scar hypertrophy in the rabbit ear model. This is associated with lower scar elevation index (SEI), lower levels of collagen I & III, higher levels of MMP1, and a higher degree of scar maturation in experimental wounds compared to controls.

scholarly journals Myofibroblast Expression in Skin Wounds Is Enhanced by Collagen III Suppression

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Mohammed M. Al-Qattan ◽  
Mervat M. Abd-Elwahed ◽  
Khalid Hawary ◽  
Maha M. Arafah ◽  
Medhat K. Shier
Keyword(s):  
Syndrome Type ◽  
Hypertrophic Scars ◽  
Hypertrophic Scarring ◽  
Ehlers Danlos Syndrome ◽  
Collagen Expression ◽  
Type Iv ◽  
Wound Model ◽  
Rabbit Ear ◽  
Collagen Iii ◽  
Danlos Syndrome

Generally speaking, the excessive expression of myofibroblasts is associated with excessive collagen production. One exception is seen in patients and animal models of Ehlers-Danlos syndrome type IV in which theCOL3A1gene mutation results in reduced collagen III but with concurrent increased myofibroblast expression. This paradox has not been examined with the use of external drugs/modalities to prevent hypertrophic scars. In this paper, we injected the rabbit ear wound model of hypertrophic scarring with two doses of a protein called nAG, which is known to reduce collagen expression and to suppress hypertrophic scarring in that animal model. The higher nAG dose was associated with significantly less collagen III expression and concurrent higher degree of myofibroblast expression. We concluded that collagen III content of the extracellular matrix may have a direct or an indirect effect on myofibroblast differentiation. However, further research is required to investigate the pathogenesis of this paradoxical phenomenon.

Human primary fibroblasts in vitro express a purinergic P2X7 receptor coupled to ion fluxes, microvesicle formation and IL-6 release

1999 ◽  
Vol 112 (3) ◽  
pp. 297-305
Author(s):  
A. Solini ◽  
P. Chiozzi ◽  
A. Morelli ◽  
R. Fellin ◽  
F. Di Virgilio
Keyword(s):  
Purinergic Receptor ◽  
Morphological Changes ◽  
Human Fibroblasts ◽  
Ion Fluxes ◽  
Disulfonic Acid ◽  
Triggered Release ◽  
Primary Fibroblasts ◽  
Purinergic P2x7 Receptor ◽  
Skin Biopsies

We have investigated reponses to extracellular ATP in human fibroblasts obtained by skin biopsies. Our data show that these cells express a P2X7 purinergic receptor, as judged by (1) RT-PCR with specific primers, (2) reactivity with a specific anti-P2X7 antiserum, (3) activation by the selective P2X agonist benzoylbenzoylATP and (4) stimulation of transmembrane ion fluxes. Stimulation with benzoylbenzoylATP, and to a lesser extent with ATP, also caused striking morphological changes and increased formation of cytoplasmic microvesicles. These changes were fully reversible upon nucleotide removal. Two known blockers of P2X receptors, oxidised ATP and pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid, inhibited the morphological changes fully and the ion fluxes partially. The residual rise in intracellular Ca2+ levels and membrane depolarization observed in the presence of the inhibitors were dependent upon activation of a P2Y-type receptor exhibiting a peculiar pharmacological profile, in that CTP was the preferred agonist. ATP stimulation triggered release of the pro-inflammatory cytokine IL-6 in fibroblasts pre-treated with PMA and bacterial endotoxin. These observations reveal a novel pathway for fibroblast activation and for their recruitment in the inflammatory response.

High-Dose Ultraviolet Light Exposure Reduces Scar Hypertrophy in a Rabbit Ear Model

2008 ◽  
Vol 121 (4) ◽  
pp. 1165-1172 ◽  
Author(s):  
Richard J. Brown ◽  
Michael J. Lee ◽  
Mark Sisco ◽  
John Y. S. Kim ◽  
Nakshatra Roy ◽  
...  
Keyword(s):  
Ultraviolet Light ◽  
Light Exposure ◽  
High Dose ◽  
Rabbit Ear ◽  
Scar Hypertrophy

Abstract 35: Enhanced Reprogramming of Human Fibroblasts into Cardiomyocytes Using Minimal Transcription Factors

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Yang Zhou ◽  
Sahar Alimohamadi ◽  
Jiandong Liu ◽  
Li Qian
Keyword(s):  
Transcription Factors ◽  
Disease Modeling ◽  
Human Fibroblasts ◽  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Clinical Applications ◽  
Significant Advance ◽  
Great Promise ◽  
Primary Fibroblasts ◽  
Core Components

The adult human heart has limited regenerative capacity and is thus an important target for novel regenerative approaches to replenish lost cardiomyocytes after cardiac injury. Cardiac reprogramming that converts fibroblasts to contractile induced cardiomyocytes (iCMs) by overexpressing cardiac lineage specific transcription factors holds great promise as an alternative approach for cardiac regeneration and disease modeling. Significant advance has been made to generate mouse iCMs; however, human iCM (hiCM) generation remains challenging and the yield is low for clinical applications. Here, we leveraged the knowledge that we learned from studying mouse iCM reprogramming to define the optimal condition for hiCM induction. We titrated the dosage of the human reprogramming factors systematically and surprisingly found the minimal core components GATA4, MEF2C and TBX5 were sufficient to induce cardiac fate in human primary fibroblasts. This is in sharp contrast to what has been reported in the literature. Subsequently, we cloned these three factors into a polycistronic vector separated by 2A peptides for defined ratio of protein expression. By optimizing the growth condition, we further improved the efficiency of hiCM reprogramming. Mechanistically, we found the balanced expression of this minimal combination of transcription factors with tailored microenvironment enhanced the establishment of cardiac program in non-myocytes. In sum, our study demonstrates that the use of a single vector with only three transcription factors simplifies generation and improves the yield of hiCMs for potential future clinical applications.

The effects of valsartan on scar maturation in an experimental rabbit ear wound model

2020 ◽  
Vol 54 (6) ◽  
pp. 382-387
Author(s):  
Muzaffer Kurt ◽  
Funda Akoz Saydam ◽  
Mehmet Bozkurt ◽  
Merdan Serin ◽  
Aysel Caglar
Keyword(s):  
Wound Model ◽  
Rabbit Ear ◽  
Scar Maturation

scholarly journals Senescence induction in human fibroblasts and hematopoietic progenitors by leukemogenic fusion proteins

Blood ◽  
2010 ◽  
Vol 115 (24) ◽  
pp. 5057-5060 ◽  
Author(s):  
Narendra Wajapeyee ◽  
Shu-Zong Wang ◽  
Ryan W. Serra ◽  
Peter D. Solomon ◽  
Arvindhan Nagarajan ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Mapk Pathway ◽  
Human Fibroblasts ◽  
Hematologic Malignancies ◽  
Dependent Manner ◽  
Epigenetic Alterations ◽  
Hematopoietic Progenitors ◽  
Damage Response ◽  
Primary Fibroblasts ◽  
Senescence Program

Abstract Hematologic malignancies are typically associated with leukemogenic fusion proteins, which are required to maintain the oncogenic state. Previous studies have shown that certain oncogenes that promote solid tumors, such as RAS and BRAF, can induce senescence in primary cells, which is thought to provide a barrier to tumorigenesis. In these cases, the activated oncogene elicits a DNA damage response (DDR), which is essential for the senescence program. Here we show that 3 leukemogenic fusion proteins, BCR-ABL, CBFB-MYH11, and RUNX1-ETO, can induce senescence in primary fibroblasts and hematopoietic progenitors. Unexpectedly, we find that senescence induction by BCR-ABL and CBFB-MYH11 occurs through a DDR-independent pathway, whereas RUNX1-ETO induces senescence in a DDR-dependent manner. All 3 fusion proteins activate the p38 MAPK pathway, which is required for senescence induction. Our results reveal diverse pathways for oncogene-induced senescence and further suggest that leukemias harbor genetic or epigenetic alterations that inactivate senescence induction genes.

Effects of Noscarna™ on hypertrophic scarring in the rabbit ear model: Histopathological aspects

2012 ◽  
Vol 35 (11) ◽  
pp. 1999-2006 ◽  
Author(s):  
Dong Won Lee ◽  
Sae Kwang Ku ◽  
Hyuk Jun Cho ◽  
Jeong Hwan Kim ◽  
Tran Tuan Hiep ◽  
...  
Keyword(s):  
Hypertrophic Scarring ◽  
Rabbit Ear

scholarly journals Inhibitory effects of essential oil from rhizomes ofLigusticum chuanxiongon hypertrophic scarring in the rabbit ear model

2011 ◽  
Vol 49 (7) ◽  
pp. 764-769 ◽  
Author(s):  
Jian-Guo Wu ◽  
Yan-Jie Wei ◽  
Xia Ran ◽  
Hong Zhang ◽  
Hua Nian ◽  
...  
Keyword(s):  
Essential Oil ◽  
Hypertrophic Scarring ◽  
Inhibitory Effects ◽  
Rabbit Ear

scholarly journals Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

2017 ◽  
Vol 5 (6) ◽  
pp. e1294 ◽  
Author(s):  
Shengxian Jia ◽  
Ping Xie ◽  
Seok J. Hong ◽  
Robert D. Galiano ◽  
Thomas A. Mustoe
Keyword(s):  
Local Application ◽  
Hypertrophic Scarring ◽  
Rabbit Ear
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