Macrophages are essential for CTGF-mediated adult β-cell proliferation after injury

Kimberly G. Riley, Raymond C. Pasek, Matthew F. Maulis, Jennifer C. Dunn, W. Reid Bolus, Peggy L. Kendall, Alyssa H. Hasty, Maureen Gannon

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Objective: Promotion of endogenous β-cell mass expansion could facilitate regeneration in patients with diabetes. We discovered that the secreted protein CTGF (aka CCN2) promotes adult β-cell replication and mass regeneration after injury via increasing β-cell immaturity and shortening the replicative refractory period. However, the mechanism of CTGF-mediated β-cell proliferation is unknown. Here we focused on whether CTGF alters cells of the immune system to enhance β-cell replication. Methods: Using mouse models for 50% β-cell ablation and conditional, β-cell-specific CTGF induction, we assessed changes in immune cell populations by performing immunolabeling and gene expression analyses. We tested the requirement for macrophages in CTGF-mediated β-cell proliferation via clodronate-based macrophage depletion. Results: CTGF induction after 50% β-cell ablation increased both macrophages and T-cells in islets. An upregulation in the expression of several macrophage and T-cell chemoattractant genes was also observed in islets. Gene expression analyses suggest an increase in M1 and a decrease in M2 macrophage markers. Depletion of macrophages (without changes in T cell number) blocked CTGF-mediated β-cell proliferation and prevented the increase in β-cell immaturity. Conclusions: Our data show that macrophages are critical for CTGF-mediated adult β-cell proliferation in the setting of partial β-cell ablation. This is the first study to link a specific β-cell proliferative factor with immune-mediated β-cell proliferation in a β-cell injury model.

Original languageEnglish
Pages (from-to)584-591
Number of pages8
JournalMolecular Metabolism
Issue number8
StatePublished - Aug 1 2015


  • CTGF
  • Macrophages
  • Proliferation
  • Regeneration
  • T-cells
  • β-cell


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