Loss of RegI in conjunction with gastrin deficiency in mice facilitates efficient gastric ulcer healing but is dispensable for hyperplasia and tumourigenesis.
ABSTRACT 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.
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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. · 19.80 Impact Factor
Conference Paper: PAM codes for optical scan intersymbol interference channel[Show abstract] [Hide abstract]
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 dBGlobal Telecommunications Conference, 1997. GLOBECOM '97., IEEE; 12/1997
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ABSTRACT: The regenerating (Reg) protein family comprises C-type lectin-like proteins discovered independently during pancreatitis and pancreatic islet regeneration. However, an increasing number of studies provide evidence of participation of Reg proteins in the proliferation and differentiation of diverse cell types. Moreover, Reg family members are associated with various pathologies, including diabetes and forms of gastrointestinal cancer. These findings have led to the emergence of key roles for Reg proteins as anti-inflammatory, antiapoptotic and mitogenic agents in multiple physiologic and disease contexts. Yet, there are significant gaps in our knowledge regarding the regulation of expression of different Reg genes. In addition, the pathways relaying Reg-triggered signals, their targets and potential cross-talk with other cascades are still largely unknown. In this review, the expression patterns of different Reg members in the pancreas and extrapancreatic tissues are described. Moreover, factors known to modulate Reg levels in different cell types are discussed. Several signaling pathways, which have been implicated in conferring the effects of Reg ligands to date, are also delineated. Further efforts are necessary for elucidating the biological processes underlying the action of Reg proteins and their involvement in various maladies. Better understanding of the function of Reg genes and proteins will be beneficial in the design and development of therapies utilizing or targeting this protein group. Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348543/Biomolecular concepts 02/2012; 3(1):57-70.