Cloning of Rat Betacellulin and Characterization of its Expression in the Gastrointestinal Tract

Chen, Xian; Dunbar, Andrew; Couper, Richard; Read, Leanna C.

doi:10.3109/08977190009003245

Cited by 11 publications

(5 citation statements)

References 17 publications

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“…It also promotes β‐cell neogenesis and improves glucose tolerance in a mouse model of diabetes (Yamamoto et al ., 2000). However, BTC is also widely expressed and additional roles in blastocyst implantation (Das et al ., 1997), gastrointestinal function (Kallincos et al ., 2000) and atherosclerosis (Tamura et al ., 2001) have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling

et al. 2003

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Heparin‐binding epidermal growth factor (HB‐EGF) and betacellulin (BTC) are activating ligands for EGF receptor (EGFR/ErbB1) and ErbB4. To identify their physiological functions, we disrupted mouse HB‐EGF and BTC alleles by homologous recombination. Most HB‐EGF−/− mice died before weaning, and survivors had enlarged, dysfunctional hearts and reduced lifespans. Although BTC−/− mice were viable and fertile and displayed no overt defects, the lifespan of double null HB‐EGF−/−/BTC−/− mice was further reduced, apparently due to accelerated heart failure. HB‐EGF−/− newborns had enlarged and malformed semilunar and atrioventricular heart valves, and hypoplastic, poorly differentiated lungs. Defective cardiac valvulogenesis was the result of abnormal mesenchymal cell proliferation during remodeling, and was associated with dramatic increases in activated Smad1/5/8. Consistent with the phenotype, HB‐EGF transcripts were localized to endocardial cells lining the margins of wild‐type valves. Similarly defective valvulogenesis was observed in newborn mice lacking EGFR and tumor necrosis factor‐α converting enzyme (TACE). These results suggest that cardiac valvulogenesis is dependent on EGFR activation by TACE‐derived soluble HB‐EGF, and that EGFR signaling is required to regulate bone morphogenetic protein signaling in this context.

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Section: Introductionmentioning

confidence: 99%

Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling

et al. 2003

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“…Fig. 1 shows the amino acid sequence alignment of the conserved EGF motif of the EGF family: human, bovine, mouse, and rat BTC (2,21,22); human and rat TGF␣ (23,24); human and mouse EGF (25,26); human heparin-biding EGF (27); human epiregurin (ER) (28); human amphiregulin (AR) (29); and human heregulin (HRG) ␤1 (30). This family shares high sequence similarity.…”

Section: Resultsmentioning

confidence: 99%

“…The essential amino acid residues for the mitogenic activity were examined in detail for EGF and TGF-␣ using recombinant DNA technology. In EGF, the importance of (21,22,37,38). In these residues, which are crucial for biological activities, Arg (41 in EGF, 42 in TGF-␣) and Leu (47 in EGF, 48 in TGF-␣) are highly conserved in the EGF family.…”

Section: Resultsmentioning

confidence: 99%

Novel Betacellulin Derivatives

Itoh

Kondo

Tanaka

et al. 2001

Journal of Biological Chemistry

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Betacellulin (BTC) is a member of the epidermal growth factor family. It has two biological activities: mitogenic activity in fibroblasts and vascular smooth muscle cells, and differentiation activity for the differentiation of pancreatic acinar AR42J cells into insulinsecreting cells. The previous finding that recombinant BTC promotes the neogenesis of ␤-cells in a mouse model supports the possibility that BTC is a therapeutic protein. However, the mitogenic activity of BTC may not be needed for differentiation into ␤-cells and may cause a side effect in clinical use. We prepared several derivatives of BTC to segregate the two activities, to decrease the mitogenic activity, and to maintain the differentiation activity. We succeeded in obtaining BTC derivatives segregated by the two biological activities by preparing truncated-type derivatives. A derivative of BTC, BTC24 -76, with a truncated N-terminal 23 amino acids and C-terminal 4 amino acids, was 2.5-fold more active in differentiation and had one-tenth of the mitogenic activity. The derivatives described in the present study should be helpful in future applications as therapeutic proteins and in basic research for discovery of a BTCspecific receptor.

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“…AREG shares a similar expression pattern with NRG1, with an enrichment in subepithelial myofibroblasts and in rare F4/80+ macrophage-enriched cells but with limited expression in the epithelium ( Inatomi et al, 2006 ; Shao and Sheng, 2010 ; Yang et al, 2017 ). EREG is also localized in an uncharacterized subpopulation of mesenchymal cells and is weakly expressed in the epithelium ( Xian et al, 1999 ; Kallincos et al, 2000 ; Xia et al, 2003 ; Lee et al, 2004 ). In contrast, BTC, HB-EGF, and TGFα are enriched in the intestinal epithelium.…”

Section: Location and Function Of Signals And Receptors During Mammalian Homeostasismentioning

confidence: 99%

Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells

Abud

Chan

Jardé

2021

Front. Cell Dev. Biol.

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Epidermal Growth Factor (EGF) has long been known for its role in promoting proliferation of intestinal epithelial cells. EGF is produced by epithelial niche cells at the base of crypts in vivo and is routinely added to the culture medium to support the growth of intestinal organoids ex vivo. The recent identification of diverse stromal cell populations that reside underneath intestinal crypts has enabled the characterization of key growth factor cues supplied by these cells. The nature of these signals and how they are delivered to drive intestinal epithelial development, daily homeostasis and tissue regeneration following injury are being investigated. It is clear that aside from EGF, other ligands of the family, including Neuregulin 1 (NRG1), have distinct roles in supporting the function of intestinal stem cells through the ErbB pathway.

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Cloning of Rat Betacellulin and Characterization of its Expression in the Gastrointestinal Tract

Cited by 11 publications

References 17 publications

Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling

Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling

Novel Betacellulin Derivatives

Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells

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