title: Kruppel-like zinc finger protein Glis2 is essential for the maintenance of normal renal functions.
abstract: To obtain insight into the physiological functions of the Krüppel-like zinc finger protein Gli-similar 2 (Glis2), mice deficient in Glis2 expression were generated. Glis2 mutant (Glis2(mut)) mice exhibit significantly shorter life spans than do littermate wild-type (WT) mice due to the development of progressive chronic kidney disease with features resembling nephronophthisis. Glis2(mut) mice develop severe renal atrophy involving increased cell death and basement membrane thickening in the proximal convoluted tubules. This development is accompanied by infiltration of lymphocytic inflammatory cells and interstitial/glomerular fibrosis. The severity of the fibrosis, inflammatory infiltrates, and glomerular and tubular changes progresses with age. Blood urea nitrogen and creatinine increase, and Glis2(mut) mice develop proteinuria and ultimately die prematurely of renal failure. A comparison of the gene expression profiles of kidneys from 25-day-old/60-day-old WT and Glis2(mut) mice by microarray analysis showed increased expressions of many genes involved in immune responses/inflammation and fibrosis/tissue remodeling in kidneys of Glis2(mut) mice, including several cytokines and adhesion and extracellular matrix proteins. Our data demonstrate that a deficiency in Glis2 expression leads to tubular atrophy and progressive fibrosis, similar to nephronophthisis, that ultimately results in renal failure. Our study indicates that Glis2 plays a critical role in the maintenance of normal kidney architecture and functions.
authors.affiliation: Division of Intramural Research, Cell Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Hong Soon
authors.initials: HS
authors.lastname: Kang
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbert
authors.forename: Ju Youn
authors.initials: JY
authors.lastname: Beak
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Collins
authors.forename: Sherry F
authors.initials: SF
authors.lastname: Grissom
authors.forename: Anton M
authors.initials: AM
authors.lastname: Jetten
mesh_terms: D000367:Age Factors; D000818:Animals; D001284:Atrophy; D002460:Cell Line; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005355:Fibrosis; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology / Q000652:urine; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011507:Proteinuria / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics
chemical_list: C430270:Gli5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins