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Published ahead of print on October 2, 2008
J Am Soc Nephrol 19: 2069-2075, 2008
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2008020162
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BRIEF COMMUNICATION

Podocyte-Specific Loss of Functional MicroRNAs Leads to Rapid Glomerular and Tubular Injury

Jacqueline Ho*,{dagger},{ddagger}, Kar Hui Ng*,{dagger},{ddagger}, Seymour Rosen§,||, Ales Dostal{ddagger},¶,**, Richard I. Gregory{ddagger},¶,** and Jordan A. Kreidberg*,{dagger},{ddagger}

Departments of * Medicine and || Pathology and Stem Cell Program, Children's Hospital Boston, Departments of {dagger} Pediatrics and ** Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and § Department of Pathology, Beth Israel Deaconess Medical Center, Boston, and {ddagger} Harvard Stem Cell Institute, Cambridge, Massachusetts

Correspondence: Dr. Jordan A. Kreidberg, Division of Nephrology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. Phone: 617-919-2959; Fax: 617-730-0129; E-mail: jordan.kreidberg{at}childrens.harvard.edu

Received for publication February 8, 2008. Accepted for publication July 1, 2008.

MicroRNAs (miRNAs) are in a class of endogenous, small, noncoding RNAs that exert their effects through posttranscriptional repression of specific target mRNAs. Although miRNAs have been implicated in the regulation of diverse biologic processes, little is known about miRNA function in the kidney. Here, mice lacking functional miRNAs in the developing podocyte were generated through podocyte-specific knockout of Dicer, an enzyme required for the production of mature miRNAs (Nphs2-Cre; Dicerflx/flx). Podocyte-specific loss of miRNAs resulted in significant proteinuria by 2 wk after birth, rapid progression of marked glomerular and tubular injury beginning at 3 wk, and death by 4 wk. Expression of the slit diaphragm proteins nephrin and podocin was decreased, and expression of the transcription factor WT1 was relatively unaffected. To identify miRNA–mRNA interactions that contribute to this phenotype, we profiled the glomerular expression of miRNAs; three miRNAs expressed in glomeruli were identified: mmu-miR-23b, mmu-miR-24, and mmu-miR-26a. These results suggest that miRNA function is dispensable for the initial development of glomeruli but is critical to maintain the glomerular filtration barrier.


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 J. Am. Soc. Nephrol.Home page
J.J. D. Ho and P. A. Marsden
Dicer Cuts the Kidney
J. Am. Soc. Nephrol., November 1, 2008; 19(11): 2043 - 2046.
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