title: Hedgehog Gli signalling in kidney fibrosis.
abstract: Kidney fibrosis is the common final pathway of virtually all progressive injury to the kidney and a promising therapeutic target in chronic kidney disease (CKD). The Hedgehog pathway has been reported to be critical in kidney development, and recent evidence suggests a role in kidney injury and fibrosis. This review provides an overview of recent data suggesting an important role of Gli transcriptional activators in kidney injury and repair. We have reported that the hedgehog transcriptional activator Gli1 specifically marks perivascular mesenchymal stem cells, which are an important source of kidney myofibroblasts. Genetic ablation of these cells ameliorated kidney and heart fibrosis and stabilized organ function after injury. Recent data suggest that Gli2 is an important driver of myofibroblast cell cycle progression and a promising therapeutic target in kidney fibrosis progression and CKD. However, the non-canonical mechanism of Gli activation in kidney fibrosis remains an open question, and further studies are needed to elucidate the role of Hedgehog Gli and Gli1+perivascular cells in human kidney fibrosis.
authors.affiliation: Division of Nephrology and Clinical Immunology, RWTH Aachen University, Pauwelstr 30, Aachen 52074, Germany.
authors.forename: Rafael
authors.initials: R
authors.lastname: Kramann
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D000071676:Zinc Finger Protein GLI1
keywords: Gli1; Gli2; hedgehog; kidney fibrosis; kidney progenitors; mesenchymal stem cells