Regulation of proximal tubular cell differentiation and proliferation in primary culture by matrix stiffness and ECM components

Wan Chun Chen, Hsi Hui Lin, Ming Jer Tang

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

To explore whether matrix stiffness affects cell differentiation, proliferation, and transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in primary cultures of mouse proximal tubular epithelial cells (mPTECs), we used a soft matrix made from monomeric collagen type I-coated polyacrylamide gel or matrigel (MG). Both kinds of soft matrix benefited primary mPTECs to retain tubularlike morphology with differentiation and growth arrest and to evade TGF-β1-induced EMT. However, the potent effect of MG on mPTEC differentiation was suppressed by glutaraldehyde-induced cross-linking and subsequently stiffening MG or by an increasing ratio of collagen in the soft mixed gel. Culture media supplemented with MG also helped mPTECs to retain tubular-like morphology and a differentiated phenotype on stiff culture dishes as soft MG did. We further found that the protein level and activity of ERK were scaled with the matrix stiffness. U-0126, a MEK inhibitor, abolished the stiff matrixinduced dedifferentiation and proliferation. These data suggest that the ERK signaling pathway plays a vital role in matrix stiffnessregulated cell growth and differentiation. Taken together, both compliant property and specific MG signals from the matrix are required for the regulation of epithelial differentiation and proliferation. This study provides a basic understanding of how physical and chemical cues derived from the extracellular matrix regulate the physiological function of proximal tubules and the pathological development of renal fibrosis.

Original languageEnglish
Pages (from-to)F695-F707
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number6
DOIs
Publication statusPublished - 2014 Sep 15

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

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