Although Hnf1α is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions.
Methodology/Principal Findings
An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway.
Conclusions/Significance
Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages. 相似文献
Follicular growth rates were studied in 5 Hereford-Holstein cross heifers on Day 14 of the oestrous cycle. The granulosa cell mitotic index (MI) was measured in non-atretic antral follicles of various diameters (0.13-8.57 mm) from Bouin-fixed ovaries collected before (199, control) and 2 h after colchicine treatment (189, treated). In control ovaries, follicles of 0.68-1.52 mm had a higher MI than those of other size classes (P less than 0.05). In colchicine-treated ovaries, the MI of follicles ranging from 0.68 to 8.57 mm increased more than that of other sized follicles, so that the mitotic time was shorter (0.78 h vs 1.32 h) in medium and large sized follicles (0.68-8.57 mm) than in smaller follicles (0.13-0.67 mm). Calculations based on the number of granulosa cells in follicles of various classes and from the time required to double the number of cells within a follicle indicate that a follicle takes 27 days to grow from 0.13 to 0.67 mm, 6.8 days from 0.68 to 3.67 mm and 7.8 days from 3.68 to 8.56 mm, indicating that growth rates varied with the size of the follicle. A period equivalent to 2 oestrous cycles would therefore be required for a follicle to grow through the antral phase, i.e. from 0.13 mm to preovulatory size. Increased MI, decreased mitotic time and increased atresia found in follicles larger than 0.68 mm could indicate a change in the follicular metabolism during its maturation. 相似文献
SPARC is a glycoprotein of the extracellular matrix that exhibits a number of biological functions such as disruption of cell adhesion and modulation of matrix metalloprotease expression. These properties, in concert with the expression of the molecule during development, repair, and neoplastic progression, suggest that SPARC has an important role in remodeling in a variety of tissues. However, the role of SPARC in the intestine is unclear since the development expression and tissular origin of SPARC in this organ appears to be species-dependent. As a first step to investigate the function of SPARC in the tissues of the intestine, we have analyzed its expression at the protein and mRNA levels in the human fetal and adult small intestinal and colonic mucosa as well as in intestinal cell models. Our results show that SPARC expression is differentially regulated during development and along the length of the human intestine. In the colon, SPARC was predominantly found at the epithelial-mesenchymal interface at the fetal stage, below detection levels in the normal adult, but re-expressed in the stroma of colonic tumors. In the small intestine, low levels of SPARC expression were observed at an early stage of morphogenesis (between 9 and 11 weeks) but expression was not detected at subsequent developmental stages nor was it induced in the mucosa of Crohn's disease. While SPARC appeared to be produced mainly by mesenchymal and stromal cells in the intact intestine it was not detected in colon cancer cells. Taken together, these results indicate that SPARC is subject to an onco-fetal pattern of expression in the stroma of the colonic mucosa while its expression is much more restricted in the small intestine, suggesting a differential involvement of this molecule in the extracellular matrix remodeling occurring along the length of the developing and diseased human intestinal mucosa. 相似文献
Only limited attention has been paid to the cell population that is affected in the course of Mouse Thymic Virus (MTV) infection. In the present study, thymic cells of newborn mice infected with MTV were examined for general ultrastructural and immunocytochemical characteristics. The earliest sign of infection was detected 5 days after inoculation. Lymphocytes, epithelial reticular cells, macrophages, and lymphoepithelial cell complexes (thymic nurse cells) were affected. Viral particles and filamentous structures were present in both the nucleus and the cytoplasm of these cells. At more advanced stages of cellular necrosis, 6 to 7 days post-infection, cytoplasmic granulation and loss in definition of cytoplasmic organelles became apparent. This was followed by nuclear degradation and cellular aggregation. The selective effect of MTV on lymphocyte subpopulations was also observed. Two populations of infected lymphocytes were identified by single and double immunogold labelling employing monoclonal antibodies and different sizes of gold particles. CD4+8+ and CD4+8- lymphocytes were found to be selectively lysed by MTV. 相似文献
The invasion of the Ponto–Caspian amphipod Dikerogammarusvillosus in European rivers is assumed to reduce macroinvertebrate diversity and to alter ecosystem functions. D.villosus shows an extraordinarily flexible feeding behavior including the ability to use various food sources. On the other hand, its response to predation risk seems to depend on environmental factors. To evaluate the ecological function of D. villosus, we estimated the daily food consumption for different food sources and analyzed potential effects of predator avoidance behavior on feeding. D.villosus consumption of willow leaves or chironomid larvae was quantified in 24-h laboratory experiments with and without kairomones of the European bullhead (Cottus gobio). Consumption rates were estimated based on gut content and gut evacuation rate under semi-natural laboratory conditions enabling the animals to feed over the whole time of the evacuation rate experiment. We observed very high evacuation rates and consequently high consumption rates up to 89% of body weight per day. Consumption rates differed significantly between food sources: D.villosus ingested more leaves than chironomid larvae. In contrast, predator cues did not affect the feeding of D. villosus. This might be explained by its strong refuge affinity and probably benefits its successful invasion. A comparison of the estimated consumption rates with results of an own consumption experiment (and other studies) under more artificial conditions indicated that more natural conditions result in higher consumption rates. Consequently, feeding rates from highly artificial experiments should be used with great caution to assess the ecosystem function of D. villosus. 相似文献
Semi-natural open habitats have drastically changed in the last few decades due to agricultural intensification and rural depopulation. Steppe-birds, and especially those adapted to primary stages of vegetation succession, are threatened by an increase in scrub cover, and management actions are being applied to reverse scrub encroachment and restore habitat suitability in semi-natural open habitats. In this paper we evaluated for the first time, the long-term effects of a wildfire on habitat structure, vegetation productivity, and the associated response of an endangered scrub-steppe specialist bird, the Dupont’s Lark Chersophilus duponti. Wildfire occurred in a Mediterranean steppe of central Spain dominated by permanent community of dwarf cushions scrubs. Bird abundance was evaluated by line transects in the burnt and unburnt areas 3 years prior to the fire and 4 and 7 years after the fire. We quantified changes in habitat structure at fine scale level through vegetation sampling points and in vegetation productivity by estimating the Normalized Difference Vegetation Index (NDVI). Fire had strong effects for at least up to 4 years after the fire, when lower NDVI values, less scrub cover and fewer, but not significant, number of males were detected in the burnt area with respect to the pre-fire conditions. Seven years after fire most vegetation variables measured did not differ between areas, number of males detected within the burnt area was recovered and NDVI values in burnt area were slightly recovered but were significantly lower than in control area. Slow regeneration of the scrub cover after fire explained the unsuccessful occupation of the burnt area by the Dupont’s Lark up to several years after fire. The more dispersed and shorter habitat created by fire 7 years after the fire seems to be more suitable for the species than that in control areas. The large number of males around the burnt area may have played a role in the recolonization process. In sum, vegetation recovery and the presence of a low scrub-steppe specialist, as the Dupont’s lark, suggests that fire management could be integrated into conservation plans to effectively manage scrub encroachment processes in Mediterranean scrub-steppes. 相似文献
Elucidating the mechanical response of diamond is a difficult task due to its ultrahard nature. Here, we applied a molecular dynamics (MD) method to investigate the mechanical response of single-crystal diamond under nanoindentation. There was no obvious “pop in” phenomenon on the load–depth curve, and the elastic modulus deduced from the curve was 1128 GPa, which was similar to the value obtained from experimental measurements. Results from computed tomography (CT) and the coordination number showed that the distribution of the mismatched C atoms around the deformation zone took the form of a ‘double cross.’ The atoms around the indenter tip could be divided into two zones, a translation zone and a lattice distortion zone, based on their movements. Subsequent first-principles calculations revealed that the C-atom displacement barrier varied significantly with direction, which resulted in shear stress between the two zones and the formation of the double-cross splitting.
