Fibrogenesis IV. Fibrosis and inflammatory bowel disease: cellular mediators and animal models

2000 ◽  
Vol 279 (4) ◽  
pp. G653-G659 ◽  
Author(s):  
Jolanta B. Pucilowska ◽  
Kristen L. Williams ◽  
P. Kay Lund
Keyword(s):  
Sulfonic Acid ◽  
Genetic Manipulation ◽  
Mesenchymal Cell ◽  
Mesenchymal Cells ◽  
Acute Injury ◽  
Ethanol Administration ◽  
Cell Phenotype ◽  
Trinitrobenzene Sulfonic Acid ◽  
Intestinal Fibrosis ◽  
Cellular Mediators

The cellular mediators of intestinal fibrosis and the relationship between fibrosis and normal repair are not understood. Identification of the types of intestinal mesenchymal cells that produce collagen during normal healing and fibrosis is vital for elucidating the answers to these questions. Acute injury may cause normal mesenchymal cells to convert to a fibrogenic phenotype that is not maintained during normal healing but may lead to fibrosis when inappropriately sustained. Proliferation of normal or fibrogenic mesenchymal cells may lead to muscularis overgrowth associated with fibrosis. The presence of increased numbers of vimentin-positive cells within fibrotic, hypertrophied muscularis in Crohn's disease suggests that changes in mesenchymal cell phenotype and number may indeed be associated with fibrosis. Fibrosis is induced in rats by peptidoglycan polysaccharides or trinitrobenzene sulfonic acid-ethanol administration, but inducing fibrosis in mice has been technically challenging. The development of current mouse models of colitis, such as dextran sodium sulfate or trinitrobenzene sulfonic acid-ethanol administration, into models of fibrosis will allow us to use genetic manipulation to study molecular mediators of fibrosis.

scholarly journals High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis

2002 ◽  
Vol 156 (5) ◽  
pp. 893-903 ◽  
Author(s):  
Safedin Beqaj ◽  
Sandhya Jakkaraju ◽  
Raymond R. Mattingly ◽  
Desi Pan ◽  
Lucia Schuger
Keyword(s):  
Smooth Muscle ◽  
Serum Response Factor ◽  
Mesenchymal Cell ◽  
Mesenchymal Cells ◽  
Small Gtpase ◽  
Cell Phenotype ◽  
Rhoa Activity ◽  
Functional Studies ◽  
Undifferentiated Mesenchymal Cell ◽  
Main Components

Round embryonic mesenchymal cells have the potential to differentiate into smooth muscle (SM) cells upon spreading/elongation (Yang, Y., K.C. Palmer, N. Relan, C. Diglio, and L. Schuger. 1998. Development. 125:2621–2629; Yang, Y., N.K. Relan, D.A. Przywara, and L. Schuger. 1999. Development. 126:3027–3033; Yang, Y., S. Beqaj, P. Kemp, I. Ariel, and L. Schuger. 2000. J. Clin. Invest. 106:1321–1330). In the developing lung, this process is stimulated by peribronchial accumulation of laminin (LN)-2 (Relan, N.K., Y. Yang, S. Beqaj, J.H. Miner, and L. Schuger. 1999. J. Cell Biol. 147:1341–1350). Here we show that LN-2 stimulates bronchial myogenesis by down-regulating RhoA activity. Immunohistochemistry, immunoblotting, and reverse transcriptase–PCR indicated that RhoA, a small GTPase signaling protein, is abundant in undifferentiated embryonic mesenchymal cells and that its levels decrease along with SM myogenesis. Functional studies using agonists and antagonists of RhoA activation and dominant positive and negative plasmid constructs demonstrated that high RhoA activity was required to maintain the round undifferentiated mesenchymal cell phenotype. This was in part achieved by restricting the localization of the myogenic transcription factor serum response factor (SRF) mostly to the mesenchymal cell cytoplasm. Upon spreading on LN-2 but not on other main components of the extracellular matrix, the activity and level of RhoA decreased rapidly, resulting in translocation of SRF to the nucleus. Both cell elongation and SRF translocation were prevented by overexpression of dominant positive RhoA. Once the cells underwent SM differentiation, up-regulation of RhoA activity induced rather than inhibited SM gene expression. Therefore, our studies suggest a novel mechanism whereby LN-2 and RhoA modulate SM myogenesis.

Mesenchyme-mediated effects of retinoic acid during rat intestinal development

1997 ◽  
Vol 110 (10) ◽  
pp. 1227-1238 ◽  
Author(s):  
M. Plateroti ◽  
J.N. Freund ◽  
C. Leberquier ◽  
M. Kedinger
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cell ◽  
Polyclonal Antibodies ◽  
Mesenchymal Cell ◽  
Mesenchymal Cells ◽  
Cell Polarization ◽  
Cell Interactions ◽  
Intestinal Cell ◽  
Cell Phenotype ◽  
Intestinal Development

In previous experiments we showed that intestinal development was dependent upon epithelial-mesenchymal cell interactions. The aim of this study was to investigate the possible role of retinoic acid (RA), a morphogenetic and differentiating agent, on the gut epithelial-mesenchymal unit. For this purpose we first analyzed the effects of a physiological dose of RA on 14-day fetal rat intestine using short-term organ culture experiments, or long-term grafts under the skin of nude mice. In these conditions, RA accelerated villus outgrowth and epithelial cell differentiation as assessed by the onset of lactase expression, and it also stimulated muscle and crypt formation. In order to analyze potential effects of RA mediated by mesenchymal cells, we isolated and characterized gut mucosa mesenchyme-derived cell cultures (mesenchyme-derived intestinal cell lines, MIC). These cells were shown to express mRNAs for retinoid binding proteins similar to those expressed in situ in the intestinal mesenchyme. MIC cells co-cultured with 14-day intestinal endoderms promoted endodermal cell adhesion and growth, and the addition of exogeneous RA enhanced epithelial cell polarization and differentiation assessed by cytokeratin and lactase immunostaining. Such a differentiating effect of RA was not observed on endodermal cells when cultured without a mesenchymal feeder layer or maintained in conditioned medium from RA-treated MIC cells. In the co-cultures, immunostaining of laminin and collagen IV with polyclonal antibodies, as well as alpha1 and beta1 laminin chains mRNAs (analyzed by RT-PCR) increased concurrently with the RA-enhanced differentiation of epithelial cells. It is worth noting that this stimulation by RA was also obvious on the mesenchymal cells cultured alone. These results show that RA plays a role in intestinal morphogenesis and differentiation. In addition, they indicate that RA acts on the mesenchymal cell phenotype and suggest that RA may modify the mesenchymal-epithelial cell interactions during intestinal development.

An ultrastructural and morphometric analysis of an in vivo contact guidance system

Development ◽  
1987 ◽  
Vol 101 (2) ◽  
pp. 363-381
Author(s):  
A. Wood ◽  
P. Thorogood
Keyword(s):  
Cell Migration ◽  
Morphometric Analysis ◽  
Mesenchymal Cell ◽  
Mesenchymal Cells ◽  
Contact Guidance ◽  
Cell Phenotype ◽  
Cell Processes ◽  
Computer Based ◽  
The Mean

The pectoral fin bud of the developing teleost embryo contains a highly ordered extracellular matrix of collagenous fibrils, called ‘actinotrichia’. During invasion of the fin fold, mesenchymal cells, migrating distally from the base of the fin, become contact aligned by the actinotrichial fibrils. Behavioural aspects of this response have previously been studied using Nomarski differential interference contrast microscopy and time-lapse video recording (Wood & Thorogood, 1984). Here we present an ultrastructural description of these cells and their matrix associations and a computer- based morphometric analysis of selected parameters within the migration substratum, relevant to this in vivo ‘contact guidance’ phenomenon. The study shows that a differentiated and aligned matrix of actinotrichial fibrils can be detected before invasion of the fin fold, at levels up to 40μm distal to the advancing mesenchymal cell margin. Subsequently, during invasion of the fin fold, aligned mesenchymal cells and processes are almost exclusively associated with actinotrichia and not the intervening surface of the epithelial basal lamina. However, aligned cell processes appear to avoid the smaller actinotrichia and at late stages of development 87á0% of actinotrichia without cell process contacts are distributed at the lower end of the size range. Study of cell ultrastructure revealed a complete absence of cytoskeletal organization within this mesenchymal cell population, although cytoskeletal components are clearly visible in adjacent epithelia. The computer-based morphometric survey of the migration substratum has shown a gradual but progressive increase in the mean diameter of actinotrichia at a level at which distal cell processes are first detectable in sections of fins. However, at similar levels over the same period the mean value for interactinotrichial spacings remained virtually constant. These results suggest that the spacing between actinotrichia is not significant in contributing to progressive changes in mesenchymal cell phenotype, but that the actinotrichia themselves are strongly implicated in providing the guidance cues to direct cell migration within the developing fin and the initiation of cell migration. These findings are discussed in the general context of cell movement and contact guidance both in vivo and in vitro.

Homocysteine Promotes Intestinal Fibrosis in Rats with Trinitrobenzene Sulfonic Acid-Induced Colitis

2014 ◽  
Vol 60 (2) ◽  
pp. 375-381 ◽  
Author(s):  
Hao Ding ◽  
Hui-Zhong Gan ◽  
Wen-Jie Fan ◽  
Li-Yu Cao ◽  
Jian-Ming Xu ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Trinitrobenzene Sulfonic Acid ◽  
Intestinal Fibrosis

scholarly journals Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds

2019 ◽  
Vol 20 (14) ◽  
pp. 3492 ◽  
Author(s):  
Rabiatul Adawiyah Razali ◽  
Yogeswaran Lokanathan ◽  
Muhammad Dain Yazid ◽  
Ayu Suraya Ansari ◽  
Aminuddin Bin Saim ◽  
...  
Keyword(s):  
Olea Europaea ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Healing Process ◽  
Mesenchymal Cell ◽  
Cell Phenotype ◽  
Wound Healing Process ◽  
Active Compounds ◽  
Mesenchymal Transition ◽  
Olea Europaéa

Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.

Inhibition of indoleamine 2,3-dioxygenase augments inflammation in the trinitrobenzene sulfonic acid (TNBS) colitis model in mice

2003 ◽  
Vol 124 (4) ◽  
pp. A486
Author(s):  
Gregory J. Gurtner ◽  
Rodney Newberry ◽  
Suzanne Shloemann ◽  
Keely McDonald ◽  
William F. Stenson
Keyword(s):  
Sulfonic Acid ◽  
Trinitrobenzene Sulfonic Acid ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tnbs Colitis ◽  
Colitis Model
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