Open AccessKrüppel-Like Zinc Finger Protein Glis2 Is Essential for the Maintenance of Normal Renal Functions
Author(s) -
Yong-Sik Kim,
Hong Soon Kang,
Ronald A. Herbert,
Ju Youn Beak,
Jennifer B. Collins,
Sherry F. Grissom,
Anton M. Jetten
Publication year - 2008
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01722-07
Subject(s) - fibrosis , biology , zinc finger , podocyte , kidney , inflammation , cancer research , medicine , endocrinology , gene , proteinuria , transcription factor , immunology , biochemistry
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 (Glis2mut ) 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. Glis2mut 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 Glis2mut 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 Glis2mut mice by microarray analysis showed increased expressions of many genes involved in immune responses/inflammation and fibrosis/tissue remodeling in kidneys of Glis2mut 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.