scholarly journals Subepithelial fibroblast cell lines from different levels of gut axis display regional characteristics

1998 ◽  
Vol 274 (5) ◽  
pp. G945-G954 ◽  
Author(s):  
Michelina Plateroti ◽  
Deborah C. Rubin ◽  
Isabelle Duluc ◽  
Renu Singh ◽  
Charlotte Foltzer-Jourdainne ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Lamina Propria ◽  
Cell Lines ◽  
Transforming Growth Factor ◽  
Mesenchymal Cell ◽  
Proximal Colon ◽  
Proximal Jejunum ◽  
Distal Small Intestine

The intestine is characterized by morphofunctional differences along the proximodistal axis. The aim of this study was to derive mesenchymal cell lines representative of the gut axis. We isolated and cloned rat intestinal subepithelial myofibroblasts raised from 8-day proximal jejunum, distal ileum, and proximal colon lamina propria. Two clonal cell lines from each level of the gut were characterized. They 1) express the specific markers vimentin, smooth muscle α-actin, and smooth muscle myosin heavy chain, revealed by immunofluorescence microscopy and 2) distinctly support endodermal cell growth in a coculture model, depending on their regional origin, and 3) the clones raised from the various proximodistal regions maintain the same pattern of morphogenetic and growth and/or differentiation factor gene expression as in vivo: hepatocyte growth and/or scatter factor and transforming growth factor-β1 mRNAs analyzed by RT-PCR were more abundant, in the colon and ileal clones and mucosal connective tissue, respectively. In addition, epimorphin mRNA studied by Northern blot was also the highest in one ileal clone, in which it was selectively upregulated by all-trans retinoic acid (RA) treatment. Epimorphin expression in isolated 8-day intestinal lamina propria was higher in the distal small intestine and proximal colon than in the proximal small intestine. In conclusion, we isolated and characterized homogeneous cell subtypes that can now be used to approach the molecular regulation of the epithelium-mesenchyme-dependent regional specificity along the gut.

Effect of Yersinia enterocolitica on intestinal mucin secretion

1989 ◽  
Vol 256 (2) ◽  
pp. G319-G327 ◽  
Author(s):  
M. Mantle ◽  
E. Thakore ◽  
J. Hardin ◽  
D. G. Gall
Keyword(s):  
Small Intestine ◽  
Yersinia Enterocolitica ◽  
Proximal Colon ◽  
Mucin Secretion ◽  
Glycoprotein Synthesis ◽  
Distal Small Intestine ◽  
Intestinal Mucin ◽  
Graded Response

Mucin and glycoprotein synthesis and secretion were evaluated in the upper, mid, and distal small intestine and in the proximal colon of rabbits infected with Yersinia enterocolitica (YE). Infected (INF) animals were examined on day 6 and compared with pair-fed controls and unmanipulated weight-matched rabbits. Tissue mucin content in vivo and mucin secretion in vitro, measured by a specific immunoassay, were significantly elevated in all four regions of the gut of INF rabbits compared with both control groups. In vitro secretion of stored glycoprotein, prelabeled with [3H]glucosamine, was not increased in the upper and mid small intestine of INF animals but was significantly elevated in the distal small intestine and proximal colon. In vitro incorporation of [14C]glucosamine was increased in all four regions of the gut of INF rabbits, but secretion of newly synthesized [14C]glycoprotein was only significantly elevated in the distal small intestine and proximal colon. A graded response was observed down the intestinal tract of INF rabbits, with the greatest increase in mucin content, synthesis and secretion occurring in the distal small intestine and proximal colon where the morphological impact of disease is also most severe.

scholarly journals LY2157299 Monohydrate, a TGF-βR1 Inhibitor, Suppresses Tumor Growth and Ascites Development in Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 260 ◽  
Author(s):  
Qing Zhang ◽  
Xiaonan Hou ◽  
Bradley Evans ◽  
Jamison VanBlaricom ◽  
Saravut Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cell Lines ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Migration And Invasion ◽  
Ascites Formation ◽  
Tgf Β1

Transforming growth factor beta (TGF-β) signaling has pleiotropic functions regulating cancer initiation, development, and metastasis, and also plays important roles in the interaction between stromal and cancer cells, making the pathway a potential therapeutic target. LY2157299 monohydrate (LY), an inhibitor of TGF-β receptor I (TGFBRI), was examined for its ability to inhibit ovarian cancer (OC) growth both in high-grade serous ovarian cancer (HGSOC) cell lines and xenograft models. Immunohistochemistry, qRT-PCR, and Western blot were performed to study the effect of LY treatment on expression of cancer- and fibroblast-derived genes. Results showed that exposure to TGF-β1 induced phosphorylation of SMAD2 and SMAD3 in all tested OC cell lines, but this induction was suppressed by pretreatment with LY. LY alone inhibited the proliferation, migration, and invasion of HGSOC cells in vitro. TGF-β1-induced fibroblast activation was blocked by LY. LY also delayed tumor growth and suppressed ascites formation in vivo. In addition, independent of tumor inhibition, LY reduces ascites formation in vivo. Using OVCAR8 xenograft specimens we confirmed the inhibitory effect of LY on TGF-β signaling and tumor stromal expression of collagen type XI chain 1 (COL11A1) and versican (VCAN). These observations suggest a role for anti-TGF-β signaling-directed therapy in ovarian cancer.

Intestinal calcium transport in the spontaneously hypertensive rat: response to calcium depletion

1986 ◽  
Vol 250 (4) ◽  
pp. G412-G419
Author(s):  
H. P. Schedl ◽  
D. L. Miller ◽  
R. L. Horst ◽  
H. D. Wilson ◽  
K. Natarajan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Calcium Transport ◽  
Spontaneously Hypertensive Rat ◽  
Calcium Depletion ◽  
Spontaneously Hypertensive ◽  
Distal Small Intestine ◽  
Wistar Kyoto

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.

scholarly journals Lineage Tracing Reveals the Dynamic Contribution of Pericytes to the Blood Vessel Remodeling in Pulmonary Hypertension

2020 ◽  
Vol 40 (3) ◽  
pp. 766-782 ◽  
Author(s):  
Jennifer Bordenave ◽  
Ly Tu ◽  
Nihel Berrebeh ◽  
Raphaël Thuillet ◽  
Amélie Cumont ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Structural Changes ◽  
Chronic Hypoxia ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Lineage Tracing ◽  
In Vivo Model ◽  
Dependent Manner

Objective: Excessive accumulation of resident cells within the pulmonary vascular wall represents the hallmark feature of the remodeling occurring in pulmonary arterial hypertension (PAH). Furthermore, we have previously demonstrated that pulmonary arterioles are excessively covered by pericytes in PAH, but this process is not fully understood. The aim of our study was to investigate the dynamic contribution of pericytes in PAH vascular remodeling. Approach and Results: In this study, we performed in situ, in vivo, and in vitro experiments. We isolated primary cultures of human pericytes from controls and PAH lung specimens then performed functional studies (cell migration, proliferation, and differentiation). In addition, to follow up pericyte number and fate, a genetic fate-mapping approach was used with an NG2CreER;mT/mG transgenic mice in a model of pulmonary arteriole muscularization occurring during chronic hypoxia. We identified phenotypic and functional abnormalities of PAH pericytes in vitro, as they overexpress CXCR (C-X-C motif chemokine receptor)-7 and TGF (transforming growth factor)-βRII and, thereby, display a higher capacity to migrate, proliferate, and differentiate into smooth muscle-like cells than controls. In an in vivo model of chronic hypoxia, we found an early increase in pericyte number in a CXCL (C-X-C motif chemokine ligand)-12-dependent manner whereas later, from day 7, activation of the canonical TGF-β signaling pathway induces pericytes to differentiate into smooth muscle-like cells. Conclusions: Our findings reveal a pivotal role of pulmonary pericytes in PAH and identify CXCR-7 and TGF-βRII as 2 intrinsic abnormalities in these resident progenitor vascular cells that foster the onset and maintenance of PAH structural changes in blood lung vessels.

Interaction of 2′,3′-di-O-nitro-5′-(N-ethylcarboxamido)adenosine with adenosine receptors in intestinal smooth muscle

1985 ◽  
Vol 63 (5) ◽  
pp. 449-452
Author(s):  
H. P. Baer ◽  
R. Vriend ◽  
A. Murji
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Adenosine Receptors ◽  
Neuroblastoma Cells ◽  
Major Effect ◽  
High Reactivity ◽  
Response Curves ◽  
Adenosine Receptor Agonists ◽  
Rabbit Small Intestine

The adenosine derivative, 2′3′-di-O-nitro-(5′-N-ethylcarboxamido)adenosine (DINECA), caused relaxation in several isolated smooth muscle preparations including guinea pig taenia caeci, beef coronary arteries, and rabbit small intestine. In rabbit small intestine the response profile of DINECA action differed from that of established adenosine receptor agonists and, in contrast with the latter, its relaxant effect was only partially reversed by the antagonist 8-p-sulfophenyltheophylline. Concentration–response curves to 5′-(N-ethylcarboxamido)adenosine (NECA), but not those to DINECA, were significantly shifted to the right by 100 μM of 8-sulfophenyltheophylline. Tissues exposed previously to DINECA became refractory to adenosine, an effect not observed with tissues exposed to NECA, suggesting that DINECA became bound to adenosine receptors. Adenylate cyclase from neuroblastoma cells, containing Ra-type adenosine receptors, was stimulated by 2-chloroadenosine and NECA but not by DINECA. The results suggest that most of the smooth muscle relaxant actions of DINECA are not due to interaction with adenosine receptors but are probably due to its function as a nitrate. However, DINECA appears to interact with adenosine receptors, causing long lasting inhibition of adenosine action in rabbit intestine. Such actions may contribute to the overall response to DINECA application in vivo, although lowering of blood pressure due to the high reactivity of the vasculature to nitrates may be the initial and major effect.

scholarly journals Maintenance of villus height and crypt depth, and enhancement of disaccharide digestion and monosaccharide absorption, in piglets fed on cows' whole milk after weaning

1996 ◽  
Vol 76 (3) ◽  
pp. 409-422 ◽  
Author(s):  
John R. Pluske ◽  
Melinda J. Thompson ◽  
Craig S. Atwood ◽  
Peter H. Bird ◽  
Ian H. Williams ◽  
...  
Keyword(s):  
Small Intestine ◽  
Live Weight ◽  
Maximum Activity ◽  
Proximal Jejunum ◽  
Villus Height ◽  
Crypt Depth ◽  
Linear Relationships ◽  
Whole Milk ◽  
And Function

The aims of the present study were (a) to maintain the structure and function of the small intestine of the piglet after weaning, and (b) to compare the capacity in vivo of sucking and weaned piglets to digest oral boluses of lactose and sucrose and absorb their monosaccharide products. Piglets were fed on cows' whole milk ad libitum every 2 h for 5 d after weaning. Physiological doses of lactose plus fructose (treatment LAC + FRU) and sucrose plus galactose (treatment SUC + GAL) were administered on day 27 of lactation and on the fifth day after weaning, after which time piglets were killed. Villus height and crypt depth were maintained (P > 0·05) by feeding cows' milk after weaning. The areas under the curves (AUC) for galactose and glucose, adjusted for live weight and plasma volume, increased (P < 0·05) after weaning. Despite the enhancement of gut function after weaning, the galactose index (Gall: AUC for galactose ingested as lactose divided by the AUC for the same dose of galactose ingested as the monosaccharide) and fructose index (FruI: AUC for fructose ingested as sucrose divide by the AUC for the same dose of fructose ingested as the monosaccharide), which are indices of digestive and absorptive efficiency, both decreased after weaning. This apparent anomaly may be reconciled by increased growth, and hence surface area, of the small intestine between weaning and slaughter such that ‘total’ digestion and absorption most probably increased despite apparent decreases in GalI and FrnI. Positive correlations (P < 0.05) between villus height and Gall are consistent with the maximum activity of lactase occurring more apically along the villus. Significant linear relationships (P < 0·05) were recorded between villus height at the proximal jejunum and adjusted AUC for galactose and glucose following treatment LAC + FRU, and between villus height at the proximal jejunum and adjusted glucose AUC following treatment SUC + GAL. These relationships suggest that maximum digestion and absorption occurs at increasing distances along the crypt:villus axis in the weaned pig.

scholarly journals Microarray interrogation of human metanephric mesenchymal cells highlights potentially important molecules in vivo

2007 ◽  
Vol 28 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Karen L. Price ◽  
David A. Long ◽  
Nipurna Jina ◽  
Helen Liapis ◽  
Mike Hubank ◽  
...  
Keyword(s):  
Cell Lines ◽  
Animal Studies ◽  
Kidney Development ◽  
Mesenchymal Cell ◽  
Cellular Processes ◽  
Embryonic Tissues ◽  
Matrix Metalloproteinase 1 ◽  
Vessel Growth ◽  
Normal Human

Many molecules have been implicated in kidney development, often based on experimental animal studies with organ cultures and cell lines. There are very few studies, however, that have directly addressed equivalent living human embryonic tissues. We generated renal mesenchymal cell lines from normal human metanephroi and used a microarray strategy to define changes in gene expression after stimulation with growth factors which enhance nephrogenesis in rodents. Changes were observed in 1) genes modulating diverse general cellular processes, such as matrix metalloproteinase 1 and stanniocalcin 1; 2) genes previously implicated in organogenesis e.g., sprouty 4 and midline 1; and 3) genes involved in blood vessel growth, including angiopoietin 1 and 4. Expression of these same genes was subsequently confirmed in vivo. Our novel data have identified several previously unhighlighted genes that may be implicated in differentiation programs within early human nephrogenesis.

scholarly journals Effects of Thymol and Thymol α-D-Glucopyranoside on Intestinal Function and Microbiota of Weaned Pigs

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 329
Author(s):  
Noémie Van Noten ◽  
Jeroen Degroote ◽  
Elout Van Liefferinge ◽  
Bernard Taminiau ◽  
Stefaan De Smet ◽  
...  
Keyword(s):  
Small Intestine ◽  
Biological Effects ◽  
Intestinal Barrier ◽  
Stomach Contents ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Intestinal Barrier Function ◽  
Distal Small Intestine ◽  
Great Relative Abundance

The present study evaluated gluco-conjugation as a measure to delay thymol absorption and enhance its antimicrobial activity in the gut of weaned piglets. The three dietary treatments consisted of a basal diet without additives (TCON), supplemented with thymol at 3.7 mmol/kg dry matter (TTHY), or with an equimolar amount of thymol α-D-glucopyranoside (TTαG). Each dietary treatment was replicated in 6 pens with 2 piglets per pen (n = 12 for analytical parameters) and was supplemented for 14 days. The total (free plus gluco-conjugated) thymol concentrations in the stomach contents were 14% lower in TTαG as compared to TTHY piglets. Neither of the additives could be detected further down the gut. E.coli counts in the proximal small intestine were significantly lower in TTHY than in TTαG pigs (3.35 vs. 4.29 log10 CFU/g); however, other bacterial counts and their metabolites were unaffected by treatment. A metagenomic bacterial analysis revealed a great relative abundance of Lactobacillus spp. in the distal small intestine (range 88.4–99.9%), irrespective of treatment. The intestinal barrier function was improved by TTHY, but not TTαG, compared to TCON. In conclusion, gluco-conjugation did not result in higher thymol concentrations in the gut, but conversely, it seemed to diminish the biological effects of thymol in vivo.

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