Gremlin1 plays a key role in kidney development and renal fibrosis

Research output: Contribution to journalArticle

Authors

  • Rachel H Church
  • Imran Ali
  • Mitchel Tate
  • Deborah Lavin
  • Arjun Krishnakumar
  • Helena M Kok
  • Philip Dunne
  • Victoria Bingham
  • Roel Goldschmeding
  • Finian Martin
  • Derek Brazil

Colleges, School and Institutes

Abstract

Gremlin1 (Grem1), an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and bone morphogenetic protein signaling is critical to normal lung, kidney, and limb development. Grem1 levels are increased in renal fibrotic conditions, including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy, and immune glomerulonephritis. We demonstrate that a small number of grem1−/− whole body knockout mice on a mixed genetic background (8%) are viable, with a single, enlarged left kidney and grossly normal histology. The grem1−/− mice displayed mild renal dysfunction at 4 wk, which recovered by 16 wk. Tubular epithelial cell-specific targeted deletion of Grem1 (TEC-grem1-cKO) mice displayed a milder response in the acute injury and recovery phases of the folic acid model. Increases in indexes of kidney damage were smaller in TEC-grem1-cKO than wild-type mice. In the recovery phase of the folic acid model, associated with renal fibrosis, TEC-grem1-cKO mice displayed reduced histological damage and an attenuated fibrotic gene response compared with wild-type controls. Together, these data demonstrate that Grem1 expression in the tubular epithelial compartment plays a significant role in the fibrotic response to renal injury in vivo.

Bibliographic note

Copyright © 2016, American Journal of Physiology-Renal Physiology.

Details

Original languageEnglish
Pages (from-to)F1141-F1157
Number of pages17
JournalAmerican Journal of Physiology - Renal Physiology
Volume312
Issue number6
Publication statusPublished - 1 Jun 2017

Keywords

  • Gremlin, kidney, renal fibrosis, development