PDGF signalling controls age-dependent proliferation in pancreatic β-cells

Hainan Chen, Xueying Gu, Yinghua Liu, Jing Wang, Stacey E. Wirt, Rita Bottino, Hubert Schorle, Julien Sage and Seung K. Kim ()
Additional contact information
Hainan Chen: Stanford University School of Medicine
Xueying Gu: Stanford University School of Medicine
Yinghua Liu: Stanford University School of Medicine
Jing Wang: Stanford University School of Medicine
Stacey E. Wirt: Stanford University School of Medicine
Rita Bottino: Children’s Hospital of Pittsburgh, University of Pittsburgh, School of Medicine
Hubert Schorle: Institute of Pathology, University of Bonn Medical School
Julien Sage: Stanford University School of Medicine
Seung K. Kim: Stanford University School of Medicine

Nature, 2011, vol. 478, issue 7369, 349-355

Abstract: Abstract Determining the signalling pathways that direct tissue expansion is a principal goal of regenerative biology. Vigorous pancreatic β-cell replication in juvenile mice and humans declines with age, and elucidating the basis for this decay may reveal strategies for inducing β-cell expansion, a long-sought goal for diabetes therapy. Here we show that platelet-derived growth factor receptor (Pdgfr) signalling controls age-dependent β-cell proliferation in mouse and human pancreatic islets. With age, declining β-cell Pdgfr levels were accompanied by reductions in β-cell enhancer of zeste homologue 2 (Ezh2) levels and β-cell replication. Conditional inactivation of the Pdgfra gene in β-cells accelerated these changes, preventing mouse neonatal β-cell expansion and adult β-cell regeneration. Targeted human PDGFR-α activation in mouse β-cells stimulated Erk1/2 phosphorylation, leading to Ezh2-dependent expansion of adult β-cells. Adult human islets lack PDGF signalling competence, but exposure of juvenile human islets to PDGF-AA stimulated β-cell proliferation. The discovery of a conserved pathway controlling age-dependent β-cell proliferation indicates new strategies for β-cell expansion.

Date: 2011
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature10502 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:478:y:2011:i:7369:d:10.1038_nature10502

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature10502

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().