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Cyst‐lining epithelial cells from ADPKD kidneys have a mechano‐ciliary dysfunction
Author(s) -
Nauli Surya,
Rossetti Sandro,
Kolb Robert,
Alenghat Francis,
Consugar Mark,
Harris Peter,
Ingber Donald,
LoghmanAdham Mahmoud,
Zhou Jing
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a339
Subject(s) - cilium , medicine , pathology , autosomal dominant polycystic kidney disease , cyst , anatomy , microbiology and biotechnology , biology
Background Studies have shown that cilia are mechanical fluid shear sensors. We have reported previously that polycystins, ADPKD proteins, play a role in mechanosensation in mouse kidney epithelial cilia. Objective The current study was designed to analyze the functions of polycystins in human cells. Methods Epithelial cells were isolated from normal and ADPKD (both normal‐looking and dilated/cystic tubules) kidneys. These cells were subject to fluid shear analysis. Results Both immortalized and primary cultured renal tubular cells originating from normal human and non‐dilated ADPKD patient kidneys displayed normal ciliary expressions of the polycystins and responded to fluid flow shear stress with a change in cytosolic calcium. In contrast, immortalized and primary cultured cyst‐lining epithelial cells from ADPKD patients with PKD1 mutation or with abnormal ciliary expression of polycystins were not responsive to fluid shear stress. Conclusion Cyst‐lining epithelia in ADPKD kidneys have lost their ciliary mechanosensing ability. Thus, we propose that loss of mechanosensation in the renal tubular epithelia is a feature of the cyst lining epithelia and monitoring cytosolic calcium in this flow assay is a useful functional readout of polycystin function. This work is supported by the NIH and PKD foundation.