Nephronophthisis

Disease mechanisms of a ciliopathy

Friedhelm Hildebrandt, Massimo Attanasio, Edgar Otto

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Nephronophthisis (NPHP), a recessive cystic kidney disease, is the most frequent genetic cause of end-stage kidney disease in children and young adults. Positional cloning of nine genes (NPHP1 through 9) and functional characterization of their encoded proteins (nephrocystins) have contributed to a unifying theory that defines cystic kidney diseases as "ciliopathies. " The theory is based on the finding that all proteins mutated in cystic kidney diseases of humans or animal models are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, and other stimuli to mechanisms of epithelial cell polarity and cell-cycle control. Mutations in NPHP genes cause defects in signaling mechanisms that involve the noncanonical Wnt signaling pathway and the sonic hedgehog signaling pathway, resulting in defects of planar cell polarity and tissue maintenance. The ciliary theory explains the multiple organ involvement in NPHP, which includes retinal degeneration, cerebellar hypoplasia, liver fibrosis, situs inversus, and mental retardation. Positional cloning of dozens of unknown genes that cause NPHP will elucidate further signaling mechanisms involved. Nephrocystins are highly conserved in evolution, thereby allowing the use of animal models to develop future therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)23-35
Number of pages13
JournalJournal of the American Society of Nephrology
Volume20
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Cystic Kidney Diseases
Cell Polarity
Cilia
Organism Cloning
Animal Models
Epithelial Cells
Genes
Situs Inversus
Centrosome
Retinal Degeneration
Wnt Signaling Pathway
Cell Cycle Checkpoints
Intellectual Disability
Liver Cirrhosis
Organelles
Chronic Kidney Failure
Young Adult
Proteins
Maintenance
Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Nephronophthisis : Disease mechanisms of a ciliopathy. / Hildebrandt, Friedhelm; Attanasio, Massimo; Otto, Edgar.

In: Journal of the American Society of Nephrology, Vol. 20, No. 1, 01.2009, p. 23-35.

Research output: Contribution to journalArticle

Hildebrandt, Friedhelm ; Attanasio, Massimo ; Otto, Edgar. / Nephronophthisis : Disease mechanisms of a ciliopathy. In: Journal of the American Society of Nephrology. 2009 ; Vol. 20, No. 1. pp. 23-35.
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