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Updated: Jul 12, 2026

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Myofibroblast- specific autophagy drives cyst growth in autosomal dominant polycystic kidney disease

Abeda Jamadar1,2, Viji Remadevi1,2, Meekha M Varghese1,2

  • 1Jared Grantham Kidney Institute, University of Kansas Medical Center, 5040 WHE, 3901 Rainbow Blvd, Kansas City, KS, USA.

Cell Communication and Signaling : CCS
|July 10, 2026
PubMed
Abstract

Insights

Autophagy in myofibroblasts drives cyst growth and fibrosis in autosomal dominant polycystic kidney disease (ADPKD). Inhibiting this process may offer a new therapeutic strategy for ADPKD patients.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Medicine

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder causing progressive kidney cyst expansion, fibrosis, and eventual kidney failure.
  • Myofibroblasts (MFs) accumulate around renal cysts, contributing to fibrosis and cyst growth, but their specific pro-cystogenic mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of autophagy within myofibroblasts (MFs) in promoting cyst expansion and fibrosis in autosomal dominant polycystic kidney disease (ADPKD).

Main Methods:

  • Assessed autophagy in human ADPKD tissues and primary cells, and in a mouse model of ADPKD using immunostaining and electron microscopy.
  • Inhibited MF autophagy pharmacologically and genetically (Atg5 deletion) in mouse models.
  • Analyzed conditioned media from ADPKD cyst epithelial cells and treated MFs with lactate, assessing HIF1α stabilization and autophagy-related gene expression.

Main Results:

  • Autophagy was detected in MFs within human and mouse ADPKD kidneys.
  • Inhibition of autophagy in MFs reduced their stimulation of cyst epithelial cell proliferation.
  • Genetic inhibition of autophagy in MFs of ADPKD mice significantly decreased cyst growth, fibrosis, and improved kidney function.
  • Lactate increased in ADPKD cyst epithelial cell media, stabilizing HIF1α in MFs and promoting autophagy.

Conclusions:

  • MF autophagy is a key driver of cyst expansion and fibrosis in ADPKD.
  • Lactate-mediated HIF1α stabilization in MFs enhances autophagy, promoting cyst epithelial growth.
  • Targeting MF-specific autophagy presents a potential therapeutic strategy for ADPKD.
Keywords:
ADPKDAutophagyFibrosisHypoxia inducible factor-1αLactateMyofibroblasts

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