Expression of Reg Family Proteins in Embryonic Stem Cells and Its Modulation by Wnt/β-Catenin Signaling

Jing, Donghui; Kehoe, Daniel E.; Tzanakakis, Emmanuel S.

doi:10.1089/scd.2009.0398

Cited by 21 publications

(23 citation statements)

References 71 publications

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“…As already mentioned, discovery of Reg expression in ESCs was recently reported (90). Considering the key roles of β-catenin/Wnt signaling in stem cell self-renewal and differentiation, we investigated whether a link between canonical Wnt and Reg exists in mESCs, similar to that in various cancer cells.…”

Section: Signaling Pathways and Reg Proteinsmentioning

confidence: 79%

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Regenerating proteins and their expression, regulation, and signaling

Parikh

Stephan

Tzanakakis³

2012

BioMolecular Concepts

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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.

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Section: Signaling Pathways and Reg Proteinsmentioning

confidence: 79%

“…The first account of Reg expression in embryonic stem cells (ESCs) was provided by Jing et al (90). When probed for different Reg genes, mouse ESCs (mESCs) showed expression of Reg1 and Reg3γ under non-differentiating conditions.…”

Section: Reg Proteins In Extrapancreatic Tissues and Cellsmentioning

confidence: 99%

Regenerating proteins and their expression, regulation, and signaling

Parikh

Stephan

Tzanakakis³

2012

BioMolecular Concepts

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“…CatL stimulates REG expression through inhibition of Ecadherin and activation of β-catenin signalling E-cadherin, which is expressed in pancreatic islets [18,19], has been shown to inhibit signalling by sequestering β-catenin [20]. Increased levels of E-cadherin during islet formation mediate a decline in the rate of beta cell proliferation [21] and REG upregulation has been linked to the activation of β-catenin [22,23]. We therefore hypothesised that the functional crosstalk between pancreatic ductal epithelium and beta cell proliferation may involve CatL-mediated activation of the Ecadherin-β-catenin pathway.…”

Section: Reg Proteins Mediate Beta Cell Proliferation In Response To mentioning

confidence: 99%

Cellular proliferation in mouse and human pancreatic islets is regulated by serpin B13 inhibition and downstream targeting of E-cadherin by cathepsin L

Lo¹,

Kryvalap²,

Sheu³

et al. 2019

Diabetologia

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Aims/hypothesis We previously reported that exposure to antibodies neutralising serpin B13, a protease inhibitor expressed in exocrine pancreatic ducts, promotes beta cell proliferation, underscoring the importance of a functional relationship between exocrine and endocrine pancreas. The aim of the present study was to identify the molecular events that link inhibition of serpin B13 to islet cell proliferation. Methods We used an in vitro culture system consisting of isolated pancreatic islets, an extract of pancreatic ductal epithelium and a monoclonal antibody (mAb) to serpin B13 or IgG isotype control. In vivo studies involved treatment of mice with these mAbs. Results The catalytic activity of cathepsin L (CatL), a cysteine protease target of serpin B13, was augmented in the pancreas of mice injected with serpin B13 mAb. Furthermore, the addition of serpin B13 mAb to the islets, together with the pancreatic ductal epithelium lysate, caused CatL-dependent cleavage of E-cadherin and concomitant upregulation of REG genes, ultimately leading to beta cell proliferation. Direct blockade of E-cadherin with mAb also markedly enhanced REG gene induction, while chemical inhibition of β-catenin, a binding target of E-cadherin, prevented the serpin B13 mAb-induced upregulation of REG genes. Conclusions/interpretation Our work implicates the CatL-E-cadherin-REG pathway in the regulation of islet cell proliferation in response to signals generated in exocrine pancreatic tissue and demonstrates that protease activity may promote adaptive changes in the islets. Data availability Microarray data that support the findings of this study have been deposited in Gene Expression Omnibus (GEO) with the accession no. GSE125151.

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“…Later, the same protein was independently cloned and sequenced from regenerating pancreatic islets (13). Analysis has revealed that PSP is expressed in various cell types in the gastrointestinal tract (14). During inflammation, PSP is up-regulated in the pancreas, the small intestine, and the stomach.…”

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confidence: 99%