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Updated: Dec 14, 2025

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress
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Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress

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Fibrocystin Is Essential to Cellular Control of Adhesion and Epithelial Morphogenesis

Wolfgang H Ziegler1, Birga Soetje1, Lisa P Marten1

  • 1Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany.

International Journal of Molecular Sciences
|July 24, 2020
PubMed

Insights

Loss of fibrocystin/polyductin (FPC) impairs epithelial cell adhesion and morphogenesis, contributing to autosomal recessive polycystic kidney disease (ARPKD). Reducing cellular tension rescues these defects, suggesting FPC influences cell interaction in kidney development.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the Pkhd1 gene.
  • Pkhd1 encodes fibrocystin/polyductin (FPC), a ciliary protein with an incompletely understood role in cell adhesion signaling.
  • The specific contributions of epithelial cell adhesion and contractility to ARPKD pathogenesis remain unclear.

Purpose of the Study:

  • To investigate the role of FPC in epithelial morphogenesis and cell adhesion.
  • To elucidate the mechanisms by which Pkhd1 mutations contribute to ARPKD.
  • To determine the impact of cellular tension on FPC-deficient epithelial development.

Main Methods:

  • Utilized a 3D cell culture epithelial morphogenesis assay with micropatterned glass coverslips.
  • Studied Pkhd1-silenced Madin-Darby Canine Kidney II (MDCKII) cells.
  • Analyzed cell adhesion, polarity, lumen formation, and centrosome positioning.
  • Applied a myosin II inhibitor to modulate cellular tension.

Main Results:

  • Pkhd1 silencing significantly reduced the formation of correctly polarized epithelial spheroids by two-thirds.
  • FPC-deficient cells exhibited altered cell adhesion and centrosome positioning during early morphogenesis.
  • Inhibition of myosin II-mediated cellular tension rescued the defective epithelial morphogenesis in Pkhd1-silenced cells.
  • These findings link FPC deficiency to impaired epithelial cell interactions and defective morphogenesis.

Conclusions:

  • Loss of FPC function leads to defective epithelial morphogenesis and altered cell contact formation.
  • Reduced cellular tension can compensate for FPC deficiency, suggesting a critical role for cell contractility.
  • Altered sensing and cell interaction of FPC-deficient epithelial cells likely promote progressive epithelial defects in ARPKD.

Keywords:
adhesion signalingepithelial polarityfibrocystinlumen formationpolycystic kidney disease

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