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Uptake and intracellular transport of the connective tissue growth factor: a potential mode of action

N A Wahab1, H Brinkman, R M Mason

  • 1Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, UK.

The Biochemical Journal
|September 21, 2001
PubMed

Insights

Connective tissue growth factor (CTGF) enters human mesangial cells via endosomes. This growth factor is then phosphorylated in the cytosol and moves to the nucleus, potentially impacting transcription.

Area of Science:

  • Cell biology
  • Molecular mechanisms of fibrotic disorders

Background:

  • Connective tissue growth factor (CTGF) is a key mediator in physiological and pathological processes.
  • CTGF is implicated in fibrotic disorders like diabetic nephropathy, but its intracellular mechanisms remain unclear.

Purpose of the Study:

  • To investigate the intracellular transport pathway of CTGF in human mesangial cells.
  • To elucidate the molecular mechanisms underlying CTGF's role in fibrotic processes.

Main Methods:

  • Utilized human mesangial cells to study CTGF internalization and localization.
  • Investigated CTGF phosphorylation by protein kinase C and the effect of PMA treatment.

Main Results:

  • Demonstrated CTGF internalization via endosomes and accumulation in a juxtanuclear organelle.
  • Showed translocation of CTGF into the cytosol, where it undergoes phosphorylation.
  • Observed nuclear translocation of phosphorylated CTGF, suggesting a role in transcription.

Conclusions:

  • Established the existence of an intracellular transport pathway for CTGF in human mesangial cells.
  • Identified cytosolic phosphorylation of CTGF, enhanced by PMA, as a key regulatory step.
  • Proposed that nuclear CTGF influences transcriptional regulation, contributing to fibrotic pathogenesis.

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