scholarly journals Sustained β-catenin activity in dermal fibroblasts promotes fibrosis by up-regulating expression of extracellular matrix protein-coding genes

2015 ◽  
Vol 235 (5) ◽  
pp. 686-697 ◽  
Author(s):  
Emily Hamburg-Shields ◽  
Gregg J DiNuoscio ◽  
Nathaniel K Mullin ◽  
Robert Lafyatis ◽  
Radhika P Atit
2016 ◽  
Vol 19 (1) ◽  
pp. 58-63 ◽  
Author(s):  
K. V Kozhina ◽  
E. N Volkova ◽  
I. N Saburina ◽  
Sergey G. Morozov ◽  
I. M Zurina ◽  
...  

He effect of mesotherapy injection (Meso-Wharton R199TM) on the dermal fibroblasts culture, simulating condition of (mature) aging skin cells are studied. Material and methods. The culture of 4th passage fibroblasts (P4), that corresponds to young skin fibroblasts (control) and the culture of 18th passage fibroblasts (P18), that has all the signs of aging dermal fibroblasts (predominance of large cells, slow cell division) were used. Bioactivity was assessed by cell morphology, epithelium-mesenchyme plasticity and expression of fibroblasts markers: cytokeratin 19, elastin, a-smooth muscle actin (aSMA), PCNA (proliferation marker), collagen types I, III, IV and fibronectin. The formation of spheroids occur when fibroblasts P18 are cultivating with the injection medication, on terms comparable to the formation of spheroids from P4 young fibroblasts. From culture of fibroblasts P18, that was cultured without medication, does not form the full spheroid, but aggregation of cells and their gradual destruction with necrotic masses within the unit are observed. The presence of the medication stimulates the “rejuvenation” of cells and subsequent recovery of the mesenchyme-epithelial plasticity of cultured fibroblasts due to the reduced ability to synthesize sufficient to establish the amount of intercellular contacts the extracellular matrix components (fibronectin and collagen), which affects the ability to form spheroids. Culturing spheroids formed with the medication stimulates expression of elastin, collagen type IV, fibronectin extracellular matrix protein that supports the skin elasticity and superficial cells actively express cytokeratin 19. The study results clearly demonstrate the effectiveness of mesotherapeutic treatment for skin rejuvenation.


2013 ◽  
Vol 7 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Noritaka Oyama ◽  
Joseph Merregaert

Extracellular matrix protein 1 (ECM1) is a secreted glycoprotein that plays a pivotal role in the structural and homeostatic biology of the skin, particularly in angiogenesis, reconstitution of basement membrane, proliferation and differentiation of epidermal keratinocytes and dermal fibroblasts, and malignant transformation. This rationale is substantiated by loss-of-function mutations in the ECM1 gene in an autosomal recessive genodermatosis lipoid proteinosis and circulating IgG autoantibodies to this molecule in a humoral autoimmune condition lichen sclerosus, both of which are counterpart disease conditions sharing comparable skin pathology. In the recent decade, considerable progress has been made in determining the in vivo function of ECM1 in animal model studies. Furthermore, underlying insights arose for the genetic predisposition in inflammatory bowel disease ulcerative colitis, acquisition of immune tolerance and allergic responses via particular T cell subsets such as CD4+CD25+ regulatory T cells and Th2 cells, regeneration of certain organs, and clinical advantages for diagnostic and prognostic significance in various cancers. Following our latest review in 2009, we now update the most recent evidences for the pleiotropic action of ECM1 in skin research, and also highlight the novel pathogenic relevance of this molecule in a variety of human disorders.


2019 ◽  
Vol 27 (12) ◽  
pp. 1858-1866 ◽  
Author(s):  
Biswajit Padhy ◽  
Ramani Shyam Kapuganti ◽  
Bushra Hayat ◽  
Pranjya Paramita Mohanty ◽  
Debasmita Pankaj Alone

2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  

Author(s):  
Aniel Moya-Torres ◽  
Monika Gupta ◽  
Fabian Heide ◽  
Natalie Krahn ◽  
Scott Legare ◽  
...  

Abstract The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems. Key points • Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1 • Biolayer interferometry allows target protein quantitation in expression media • High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality Graphical abstract


2002 ◽  
Vol 267 (4) ◽  
pp. 440-446 ◽  
Author(s):  
A. Kapetanopoulos ◽  
F. Fresser ◽  
G. Millonig ◽  
Y. Shaul ◽  
G. Baier ◽  
...  

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