Gremlin1 plays a key role in kidney development and renal fibrosis

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

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Abstract

Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling 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. 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. Grem1-/- mice displayed mild renal dysfunction at 4 wk, which recovered by 16 wk. Tubular epithelial specific targeted deletion of Grem1 (Grem1-TEC-/-) mice displayed a milder response in both the acute injury and recovery phase of the folic acid model. Grem1-TEC-/- mice had smaller increases in indices of kidney damage compared to wild-type. In the recovery phase of the folic acid model, associated with renal fibrosis, Grem1-TEC-/- mice displayed reduced histological damage and an attenuated fibrotic gene response compared to wild-type controls. Together, these data demonstrated that Grem1 expression in the tubular epithelial compartment plays a significant role in the fibrotic response to renal injury in vivo.
Original languageEnglish
JournalAmerican journal of physiology. Renal physiology
DOIs
Publication statusPublished - 18 Jan 2017

Keywords

  • Journal Article

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