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TGF-β1 Up-Regulates Connective Tissue Growth Factor Expression in Human Granulosa Cells through Smad and ERK1/2

Jung-Chien Cheng1, Hsun-Ming Chang1, Lanlan Fang2

  • 1Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.

Plos One
|May 9, 2015
PubMed

Insights

Transforming growth factor-beta 1 (TGF-β1) up-regulates connective tissue growth factor (CTGF) in human granulosa cells. This regulation involves Smad2, Smad3, and ERK1/2 signaling pathways, offering insights into ovarian function.

Area of Science:

  • Reproductive biology
  • Cellular signaling
  • Molecular endocrinology

Background:

  • Connective tissue growth factor (CTGF, also known as CCN2) is a secreted protein regulating cellular functions.
  • In the ovary, CTGF is crucial for follicular development, ovulation, and luteinization, primarily in granulosa cells.
  • Transforming growth factor-beta 1 (TGF-β1) up-regulates CTGF in animal granulosa cells, but the mechanism in humans is unknown.

Purpose of the Study:

  • To investigate whether TGF-β1 up-regulates CTGF expression in human granulosa cells.
  • To elucidate the molecular mechanisms underlying TGF-β1-induced CTGF expression in human granulosa cells.

Main Methods:

  • Treatment of immortalized and primary human granulosa cells with TGF-β1.
  • siRNA-mediated knockdown of Smad2, Smad3, and ERK1/2.
  • Pharmacological inhibition of Smad2, Smad3, and ERK1/2 pathways.

Main Results:

  • TGF-β1 treatment significantly up-regulated CTGF expression in both immortalized and primary human granulosa cells.
  • Inhibition of Smad2, Smad3, or ERK1/2 pathways attenuated the TGF-β1-induced increase in CTGF expression.
  • These findings indicate that Smad2, Smad3, and ERK1/2 are key mediators of TGF-β1's effect on CTGF.

Conclusions:

  • TGF-β1 stimulates CTGF expression in human granulosa cells through Smad2/3 and ERK1/2 signaling pathways.
  • This study elucidates critical molecular mechanisms of CTGF regulation in the human ovary.
  • Understanding these pathways provides insights into human reproductive processes and potential therapeutic targets.

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