2019
DOI: 10.3389/fcell.2019.00235
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Four Decades After the Discovery of Regenerating Islet-Derived (Reg) Proteins: Current Understanding and Challenges

Abstract: Regenerating islet-derived (Reg) proteins have emerged as multifunctional agents with pro-proliferative, anti-apoptotic, differentiation-inducing and bactericidal properties. Over the last 40 years since first discovered, Reg proteins have been implicated in a gamut of maladies including diabetes, various types of cancer of the digestive tract, and Alzheimer disease. Surprisingly though, a consensus is still absent on the regulation of their expression, and molecular underpinning of their function. Here, we pr… Show more

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Cited by 77 publications
(82 citation statements)
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References 165 publications
(248 reference statements)
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“…Reg-1α induces mouse embryonic stem cells (mESCs) to acquire an endoderm-like phenotype (Jing et al, 2010) and restrains proliferation of gastrointestinal cell types (for review Chen et al, 2019) suggesting a possible general role of this protein in cell differentiation. Our study supports this idea.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Reg-1α induces mouse embryonic stem cells (mESCs) to acquire an endoderm-like phenotype (Jing et al, 2010) and restrains proliferation of gastrointestinal cell types (for review Chen et al, 2019) suggesting a possible general role of this protein in cell differentiation. Our study supports this idea.…”
Section: Discussionmentioning
confidence: 99%
“…On the basis of this information and on the observation that Reg-1α acts as differentiation factor for different cell types (Jing et al, 2010;Parikh et al, 2012;Chen et al, 2019), here we have investigated the potential function of Reg-1α on migration and differentiation of neural precursor cells. Using neurosphere cultures and in utero electroporation, we show that Reg-1α increases migration and differentiation of rodent neural and cortical precursors through the GSK-3β/β-catenin pathway and promotes the in vivo differentiation of cortical precursors, thereby modifying their migration.…”
Section: Introductionmentioning
confidence: 99%
“…The role of EXTL3 in Reg1-signaling has yet to be sufficiently demonstrated [34]. Direct interaction between Reg1 and AExtl3 has not been shown conclusively via immunoprecipitation or other methods.…”
Section: Novel Function Of Extl3 As a Cell Surface Receptormentioning
confidence: 99%
“…REG3A was shown to activate the EXTL3-PI3K-AKT signaling pathway to regulate keratinocyte proliferation and/or differentiation [43]. However, the role of EXTL3 in REG3A signaling is also debatable [34]. The amount of HS on the keratinocyte cell surface and in the wound environment is very low, but the predominant glycosaminoglycan in the skin is dermatan sulfate, which can act as a coreceptor for fibroblast growth factor 7 [44].…”
Section: Novel Function Of Extl3 As a Cell Surface Receptormentioning
confidence: 99%
“…Regenerating (Reg) family members have been shown to promote proliferation and differentiation, and prevent apoptosis in diverse cell types in different contexts [95]. It was reported that the levels of serum REG1A were increased in diabetes patients [96].…”
Section: Reg1mentioning
confidence: 99%