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Title

Connective Tissue Growth Factor Modulates Adult β-Cell Maturity and Proliferation to Promote β-Cell Regeneration in Mice

Authors
Riley, Kimberly G
Pasek, Raymond C
Maulis, Matthew F
Peek, Jennifer
Brigstock, David R
Gannon, Maureen
Published in Diabetes. 2015, vol. 64, no. 4, p. 1284-98
Abstract Stimulation of endogenous β-cell expansion could facilitate regeneration in patients with diabetes. In mice, connective tissue growth factor (CTGF) is expressed in embryonic β-cells and in adult β-cells during periods of expansion. We discovered that in embryos CTGF is necessary for β-cell proliferation, and increased CTGF in β-cells promotes proliferation of immature (MafA(-)) insulin-positive cells. CTGF overexpression, under nonstimulatory conditions, does not increase adult β-cell proliferation. In this study, we tested the ability of CTGF to promote β-cell proliferation and regeneration after partial β-cell destruction. β-Cell mass reaches 50% recovery after 4 weeks of CTGF treatment, primarily via increased β-cell proliferation, which is enhanced as early as 2 days of treatment. CTGF treatment increases the number of immature β-cells but promotes proliferation of both mature and immature β-cells. A shortened β-cell replication refractory period is also observed. CTGF treatment upregulates positive cell-cycle regulators and factors involved in β-cell proliferation, including hepatocyte growth factor, serotonin synthesis, and integrin β1. Ex vivo treatment of whole islets with recombinant human CTGF induces β-cell replication and gene expression changes consistent with those observed in vivo, demonstrating that CTGF acts directly on islets to promote β-cell replication. Thus, CTGF can induce replication of adult mouse β-cells given a permissive microenvironment.
Identifiers
PMID: 25392241
Full text
Article (Published version) (2.9 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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RILEY, Kimberly G et al. Connective Tissue Growth Factor Modulates Adult β-Cell Maturity and Proliferation to Promote β-Cell Regeneration in Mice. In: Diabetes, 2015, vol. 64, n° 4, p. 1284-98. https://archive-ouverte.unige.ch/unige:55457

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Deposited on : 2015-04-13

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