Loss of RegI in conjunction with gastrin deficiency in mice facilitates efficient gastric ulcer healing but is dispensable for hyperplasia and tumourigenesis
GRIP Lab (Gastrointestinal Research, Inflammation & Pathology), Murdoch Children's Research Institute, Parkville 3052, Australia. Regulatory Peptides
(Impact Factor: 1.83).
12/2009; 160(1-3):9-18. DOI: 10.1016/j.regpep.2009.12.001
RegI (Regenerating islet derived-1) was originally characterized as a growth factor involved in pancreatic islet cell regeneration. It is also considered a gastrointestinal mitogen as its expression is increased during pathologies involving aberrant cell proliferation that can lead to neoplasia. However, the absolute requirement for RegI to directly stimulate gastric mucosal cell proliferation in vivo requires further investigation. We used RegI-deficient mice to determine the requirement for RegI in normal gastric mucosal development, wound healing, hyperplasia and tumourigenesis. We found that epithelial repair of acetic acid ulcers in compound mutant RegI/gastrin-deficient mice was significantly reduced compared to wild type, RegI-deficient or gastrin-deficient mice. In contrast, RegI was dispensable for normal gastric mucosal development, hyperplasia in HKbeta-deficient mice and tumourigenesis in gp130(F/F) mice. Although RegI was not required for proliferation in these pathological models, expression of multiple Reg family members were increased during gp130(F/F) tumourigenesis. Interestingly, loss of RegI in gp130(F/F) mice resulted in decreased expression of other Reg family members. Our results indicate that RegI and gastrin may synergistically regulate gastric mucosal proliferation during certain pathological settings like wound healing while gastric epithelial proliferation in other pathologies may require coordinated expression of multiple Reg genes.
Available from: Anne Brüstle
- "RNA was precipitated with LiCl 2 and cDNA synthesis was performed (iScript kit; Bio-Rad, Mississauga, ON). Previously published primers (Peterson et al., 2010) or primers selected from the primerbank (Spandidos et al., 2008) (Table S2) were used in qRT-PCR with SyberGreen master mix (ABI). Data were analyzed by the À2DDCT method normalizing to gapdh. "
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ABSTRACT: Thymic stromal lymphopoetin (TSLP) influences numerous immune functions, including those in the colonic mucosa. Here we report that TSLP-deficient (Tslp(-/-)) mice did not exhibit increased inflammation during dextran sodium sulfate (DSS)-induced colitis but failed to recover from disease, resulting in death. Increased localized neutrophil elastase (NE) activity during overt inflammation was observed in Tslp(-/-) mice and was paralleled by reduced expression of an endogenous inhibitor, secretory leukocyte peptidase inhibitor (SLPI). Pharmacological inhibition of NE or treatment with rSLPI reduced DSS-induced mortality in Tslp(-/-) mice. Signaling through TSLPR on nonhematopoietic cells was sufficient for recovery from DSS-induced colitis. Expression of the receptor occurred on intestinal epithelial cells (IEC), with stimulation inducing SLPI expression. Therefore, TSLP is critical in mediating mucosal healing after insult and functions in a nonredundant capacity that is independent of restraining T helper 1 (Th1) and Th17 cell cytokine production.
Immunity 08/2011; 35(2):223-35. DOI:10.1016/j.immuni.2011.05.015 · 21.56 Impact Factor
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ABSTRACT: Multilevel amplitude modulation codes over noisy optical scan
channel modeled by 1+4D+D<sup>2</sup> are described. Even though this
channel is as good as the perfect response (no ISI) channel if a maximum
likelihood sequence estimator (MLSE) based on the channel trellis is
employed, conventional trellis coded modulation (TCM) cannot guarantee
large coding gains due to the channel memory. To avoid the channel input
error sequences which lead to small differences of the Euclidean
distance in the channel trellis, a nonlinear block code as an inner code
can be designed with some bandwidth expansion. With two sets of
nonlinear block codes, a simple multiple trellis code whose edges are
labeled from an inner code is constructed as an outer code to increase
the minimum Euclidean distance further in the decoder trellis, combining
the trellis of the encoder and channel as one. The inner codes have many
desirable features such as large coding gains, low decoding complexity
and good synchronization property as well as mitigating the channel ISI
problem. With the slight expense of the decoding complexity and some
data rate loss with respect to an uncoded MLSE system, this multiple TCM
scheme offers approximately asymptotic coding gains of about 6 to 9 dB
Global Telecommunications Conference, 1997. GLOBECOM '97., IEEE; 12/1997
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ABSTRACT: l-Carnosine coated iron oxide nanoparticles (CCIO NPs) have been prepared via co-precipitation of iron oxide in the presence of l-carnosine. Crystalline phase was identified as magnetite with an average crystallite size of 8nm as estimated from X-ray line profile fitting. Particle size estimated from TEM by log-normal fitting was ∼11nm. FTIR analysis showed that the binding of carnosine onto the surface of iron oxide is through unidentate linkage of carboxyl group. CCIO NPs showed superparamagnetic charactersitic at room temperature. The magnetic core size of superparamagnetic CCIO NPs was found slightly smaller than the size obtained from TEM, due to the presence of magnetically dead layer. Magnetization measurements revealed that l-carnosine iron oxide composite has immeasurable coercivity and remanence with absence of hysteritic behavior, which implies superparamagnetic behavior at room temperature. The low value of saturation magnetization compared to the bulk magnetite has been explained by spin canting. LDH activity tests showed slight cytotoxicity of high dose of CCIO NPs. The ac conductivity of CCIO NPs was found to be greater than that of carnosine and the effective conduction mechanism was found as correlated barrier hopping (CBH). dc activation energy of the product at around room temperature was measured as 0.312eV which was in good agreement with the earlier reports.
Journal of Alloys and Compounds 02/2011; 509(5):2555-2561. DOI:10.1016/j.jallcom.2010.11.088 · 3.00 Impact Factor
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