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Calponin 1 contributes to myofibroblast differentiation of human pleural mesothelial cells

Young-Yeon Choo1, Tsuyoshi Sakai1, Satoshi Komatsu1

  • 1Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|January 12, 2022
PubMed

Insights

Calponin 1 upregulation drives contractile myofibroblast differentiation in human pleural mesothelial cells (HPMCs). This process is key to pleural fibrosis development and scar tissue stiffening.

Area of Science:

  • Cell Biology
  • Connective Tissue Research
  • Pulmonary Medicine

Background:

  • Pleural mesothelial cells (PMCs) transform into myofibroblasts through mesothelial-mesenchymal transition (MesoMT), contributing to pleural fibrosis.
  • The precise mechanisms by which these transformed cells drive lung fibrosis are not fully understood.

Purpose of the Study:

  • To investigate the mechanism of contractile myofibroblast differentiation in PMCs.
  • To elucidate the role of calponin 1 in this differentiation process and its contribution to pleural fibrosis.

Main Methods:

  • Human PMCs (HPMCs) were treated with transforming growth factor-β (TGF-β).
  • Calponin 1 expression levels were modulated using gene silencing techniques.
  • Cytoskeletal rearrangement, stress fiber formation, and cellular contractility were assessed.

Main Results:

  • TGF-β significantly upregulated calponin 1 expression and induced cytoskeletal rearrangement with stress fiber formation in HPMCs.
  • Downregulation of calponin 1 reduced stress fiber formation and cellular contractility.
  • Stress fibers were primarily composed of α-smooth muscle actin (αSMA) associated with calponin 1, myosin II, and α-actinin, with aligned focal adhesions.

Conclusions:

  • Calponin 1 facilitates the formation of contractile stress fibers in HPMCs, resembling myofibrils.
  • Upregulation of calponin 1 is central to the differentiation of HPMCs into contractile myofibroblasts.
  • This differentiation contributes to pleural tissue stiffening and the progression of pleural fibrosis.
Keywords:
calponinmesothelial mesenchymal transitionpleural fibrosisstress fiberα-smooth muscle actin

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