ArticleCell cycle (Georgetown, Tex.)2013
Overexpression of E2F3 promotes proliferation of functional human β cells without induction of apoptosis.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Identification of reversible and druggable pathways to improve beta-cell function and survival in Type 2 diabetes.Islets · 2023Article
- Small RNA Sequencing Analysis of STZ-Injured Pancreas Reveals Novel MicroRNA and Transfer RNA-Derived RNA with Biomarker Potential for Diabetes Mellitus.International journal of molecular sciences · 2023Article
- ISL1 controls pancreatic alpha cell fate and beta cell maturation.Cell & bioscience · 2023Article
- MicroRNA‑141 inhibits the differentiation of bone marrow‑derived mesenchymal stem cells in steroid‑induced osteonecrosis via E2F3.Molecular medicine reports · 2022Article
- Smad3 deficiency improves islet-based therapy for diabetes and diabetic kidney injury by promoting β cell proliferationTheranostics · 2022Article
- The Transcriptome and Epigenome Reveal Novel Changes in Transcription Regulation During Pancreatic Rat Islet Maturation.Endocrinology · 2021Article
- Single-Cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model.iScience · 2020Article
- Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression.Journal of cellular and molecular medicine · 2020Article
- miR-378a-5p and miR-630 induce lens epithelial cell apoptosis in cataract via suppression of E2F3.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Resveratrol Attenuates High Glucose-Induced Vascular Endothelial Cell Injury by Activating the E2F3 Pathway.BioMed research international · 2020Article
- Age-related transcriptome changes in Sox2+ supporting cells in the mouse cochlea.Stem cell research & therapy · 2019Article
- miR‑145 suppresses ovarian cancer progression via modulation of cell growth and invasion by targeting CCND2 and E2F3.Molecular medicine reports · 2019Article
- MicroRNA-432 targeting E2F3 and P55PIK inhibits myogenesis through PI3K/AKT/mTOR signaling pathway.RNA biology · 2017Article
- Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway.Oncotarget · 2016Article
- miR-874 suppresses the proliferation and metastasis of osteosarcoma by targeting E2F3.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Cdk5r1 Overexpression Induces Primary β-Cell Proliferation.Journal of diabetes research · 2016Article
- WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability.Endocrine journal · 2015Article
- miR-141 suppresses the growth and metastasis of HCC cells by targeting E2F3.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Article
Corrections and comments
- Erratum issuedCorrigendum.2016
Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
The mechanisms that control proliferation, or lack thereof, in adult human β cells are poorly understood. Controlled induction of proliferation could dramatically expand the clinical application of islet cell transplantation and represents an important component of regenerative approaches to a functional cure of diabetes. Adult human β cells are particularly resistant to common proliferative targets and often dedifferentiate during proliferation. Here we show that expression of the transcription factor E2F3 has a role in regulating β-cell quiescence and proliferation. We found human islets have virtually no expression of the pro-proliferative G 1/S transcription factors E2F1-3, but an abundance of inhibitory E2Fs 4-6. In proliferative human insulinomas, inhibitory E2Fs were absent, while E2F3 is expressed. Using this pattern as a "roadmap" for proliferation, we demonstrated that ectopic expression of nuclear E2F3 induced significant expansion of insulin-positive cells in both rat and human islets. These cells did not undergo apoptosis and retained their glucose-responsive insulin secretion, showing the ability to reverse diabetes in mice. Our results suggest that E2F4-6 may help maintain quiescence in human β cells and identify E2F3 as a novel target to induce proliferation of functional β cells. Refinement of this approach may increase the islets available for cell-based therapies and research and could provide important cues for understanding in vivo proliferation of β cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.