Perinatal survivin is essential for the establishment of pancreatic beta cell mass in mice

Wu, Xiaohong; Wang, L.; Schroer, Stephanie A.; Choi, Diana; Chen, P.; Okada, Hitoshi; Woo, Minna

doi:10.1007/s00125-009-1469-6

Cited by 28 publications

(31 citation statements)

References 53 publications

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“…Survivin expression is very low in adult mouse islets but becomes upregulated during pregnancy and after pancreatic duct ligation [6], [33]. Mice lacking survivin in β-cells develop insulin-deficient diabetes after birth due to a failure of β-cell mass expansion [34], [35] and show defective β-cell mass expansion and proliferation after pancreatic injury [33]. On the other hand, overexpression of survivin does not induce β-cell proliferation but improves survival of islet grafts [36].…”

Section: Discussionmentioning

confidence: 99%

EGFR Signaling Promotes β-Cell Proliferation and Survivin Expression during Pregnancy

et al. 2014

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Placental lactogen (PL) induced serotonergic signaling is essential for gestational β-cell mass expansion. We have previously shown that intact Epidermal growth factor –receptor (EGFR) function is a crucial component of this pathway. We now explored more specifically the link between EGFR and pregnancy-induced β-cell mass compensation. Islets were isolated from wild-type and β-cell-specific EGFR-dominant negative mice (E1-DN), stimulated with PL and analyzed for β-cell proliferation and expression of genes involved in gestational β-cell growth. β-cell mass dynamics were analyzed both with traditional morphometrical methods and three-dimensional optical projection tomography (OPT) of whole-mount insulin-stained pancreata. Insulin-positive volume analyzed with OPT increased 1.4-fold at gestational day 18.5 (GD18.5) when compared to non-pregnant mice. Number of islets peaked by GD13.5 (680 vs 1134 islets per pancreas, non-pregnant vs. GD13.5). PL stimulated beta cell proliferation in the wild-type islets, whereas the proliferative response was absent in the E1-DN mouse islets. Serotonin synthesizing enzymes were upregulated similarly in both the wild-type and E1-DN mice. However, while survivin (Birc5) mRNA was upregulated 5.5-fold during pregnancy in the wild-type islets, no change was seen in the E1-DN pregnant islets. PL induced survivin expression also in isolated islets and this was blocked by EGFR inhibitor gefitinib, mTOR inhibitor rapamycin and MEK inhibitor PD0325901. Our 3D-volumetric analysis of β-cell mass expansion during murine pregnancy revealed that islet number increases during pregnancy. In addition, our results suggest that EGFR signaling is required for lactogen-induced survivin expression via MAPK and mTOR pathways.

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Section: Discussionmentioning

confidence: 99%

EGFR Signaling Promotes β-Cell Proliferation and Survivin Expression during Pregnancy

et al. 2014

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“…As shown by embryonic lethality in mice with survivin locus disruption that it plays a critical in overall normal embryonic development [32]. In adults, survivin is absent in most of the terminally differentiated tissues as opposed to it high re-expression in malignant cells.…”

Section: Survivinmentioning

confidence: 99%

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Khan

Yadav

et al. 2017

Cell Mol Biol Lett

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Squamous cell carcinoma (SCC) is the most common cancer worldwide. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy. Despite aggressive multimodal treatment, most of the patients relapse. Identification of molecules that sustain cancer cell growth and survival has made molecular targeting a feasible therapeutic strategy. Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family, which is overexpressed in most of the malignancies including SCC and totally absent in most of the normal tissues. This feature makes survivin an ideal target for cancer therapy. It orchestrates several important mechanisms to support cancer cell survival including inhibition of apoptosis and regulation of cell division. Overexpression of survivin in tumors is also associated with poor prognosis, aggressive tumor behavior, resistance to therapy, and high tumor recurrence. Various strategies have been developed to target survivin expression in cancer cells, and their effects on apoptosis induction and tumor growth attenuation have been demonstrated. In this review, we discuss recent advances in therapeutic potential of survivin in cancer treatment.

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“…Blockade of this miRNA had a strong effect on a set of genes playing key roles in β cell proliferation and survival. Birc5 (also known as Survivin) and Foxm1 were among the most interesting genes upregulated in β cells upon blockade of miR-338-3p: the former has antiapoptotic and proproliferative properties, and the latter promotes β cell proliferation (19,54). Both have been shown to increase in islets from animal models characterized by β cell expansion and regeneration, such as pregnant mice at day 14 of gestation and ob/ob mice (16,19,55).…”

Section: Figurementioning

confidence: 99%

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

Jacovetti¹,

Abderrahmani²,

Parnaud³

et al. 2012

J. Clin. Invest.

157

168

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Pregnancy and obesity are frequently associated with diminished insulin sensitivity, which is normally compensated for by an expansion of the functional β cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory β cell mass expansion is largely unknown. We found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein-coupled estrogen receptor GPR30 and the glucagon-like peptide 1 (GLP1) receptor. Blockade of miR-338-3p in β cells using specific anti-miR molecules mimicked gene expression changes occurring during β cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory β cell mass expansion occurring under different insulin resistance states.

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Perinatal survivin is essential for the establishment of pancreatic beta cell mass in mice

Cited by 28 publications

References 53 publications

EGFR Signaling Promotes β-Cell Proliferation and Survivin Expression during Pregnancy

EGFR Signaling Promotes β-Cell Proliferation and Survivin Expression during Pregnancy

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

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