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Modulation of the expression of connective tissue growth factor by alterations of the cytoskeleton

Christian Ott1, Dominika Iwanciw, Angela Graness

  • 1Medizinische Klinik IV, Universität Erlangen-Nürnberg, Loschgestrasse 8, D-91054 Erlangen, Germany.

The Journal of Biological Chemistry
|September 3, 2003
PubMed

Insights

Cytoskeletal changes regulate connective tissue growth factor (CTGF) expression. Microtubule disruption and RhoA activation increase CTGF, while G-actin levels inversely correlate with CTGF, linking cytoskeleton dynamics to CTGF regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Connective tissue growth factor (CTGF, also known as CCN2) plays a crucial role in various cellular processes.
  • The regulation of CTGF expression is complex and influenced by cellular environmental cues.
  • Cytoskeletal architecture is increasingly recognized as a modulator of gene expression.

Purpose of the Study:

  • To investigate the relationship between cytoskeletal dynamics and CTGF gene expression.
  • To elucidate the role of microtubule and actin cytoskeleton, as well as RhoA signaling, in CTGF regulation.
  • To understand the molecular mechanisms underlying CTGF upregulation in response to mechanical stress.

Main Methods:

  • Treatment of cells with microtubule-disrupting agents (nocodazole, colchicine) and stabilizers (paclitaxel).
  • Assessment of RhoA activation and actin stress fiber formation.
  • Interference with RhoA signaling pathways using pharmacological inhibitors (simvastatin, toxinB, C3 toxin, Y27632).
  • Disruption of the actin cytoskeleton using latrunculin B and cytochalasin D.

Main Results:

  • Microtubule disruption significantly upregulated CTGF expression, an effect abolished by microtubule stabilization.
  • RhoA activation and actin stress fiber stabilization were consequences of microtubule disruption and correlated with CTGF induction.
  • Inhibition of RhoA signaling prevented CTGF upregulation.
  • Latrunculin B interfered with nocodazole-induced CTGF upregulation, while cytochalasin D increased CTGF expression, suggesting a role for G-actin levels.

Conclusions:

  • Alterations in both microtubule and actin cytoskeletons are linked to CTGF expression.
  • RhoA signaling is a key mediator in the pathway from cytoskeletal changes to CTGF induction.
  • The inverse relationship between G-actin levels and CTGF expression provides a novel insight into CTGF regulation.
  • These findings offer a molecular basis for elevated CTGF in cells experiencing mechanical stress.

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