Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Fibrosis

GLI2 inhibition reduces myofibroblast generation and kidney fibrosis

Nature Reviews Nephrology volume 11, page 568 (2015)Cite this article

Subjects

Benjamin Humphreys and colleagues previously showed that GLI1+ perivascular cells are a mesenchymal stem cell (MSC)-like progenitor population that generates myofibroblasts after kidney injury. In their new study they investigated the functional role of Hh–GLI signalling in these progenitors during fibrosis. “We believe that understanding how fibrosis occurs will lead to new treatments for patients with kidney disease,” explains Humphreys. “The aim of our study was to provide proof-of-principle for this concept.”

The researchers found that conditional knockout or inhibition of GLI2, but not GLI1, in cultured MSC-like progenitor cells induced cell-cycle arrest, whereas GLI2 overexpression activated Hh signalling and increased cell proliferation. In mice, GLI1 and GLI2 were specifically upregulated in cells of the myofibroblast lineage after kidney injury induced by unilateral ureteral obstruction. Conditional knockout of Gli2 in GLI1+ cells or pharmacological inhibition of GLI2 induced myofibroblast cell-cycle arrest and reduced kidney fibrosis in this model. “Targeting GLI2 is an effective strategy to prevent myofibroblast proliferation and slow kidney disease progression in mice,” says Humphreys.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Kramann, R. et al. Pharmacological GL12 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis. J. Clin. Invest. 10.1172/JCI174929

Download references

Authors
  1. Ellen F. Carney
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carney, E. GLI2 inhibition reduces myofibroblast generation and kidney fibrosis. Nat Rev Nephrol 11, 568 (2015). https://doi.org/10.1038/nrneph.2015.135

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nrneph.2015.135

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing