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Low-density lipoprotein-related receptor protein 1 (LRP-1) is not required for insulin-like growth factor binding

M S Pampusch1, E Kamanga-Sollo, M R Hathaway

  • 1Animal Growth and Development Laboratory, Department of Animal Science, University of Minnesota, 1354 Eckles Ave., St. Paul, MN 55108, USA.

Domestic Animal Endocrinology
|March 1, 2011
PubMed

Insights

Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits cell proliferation. This study found the low-density lipoprotein receptor-related protein-1 (LRP-1) is not required for IGFBP-3 to suppress myogenic cell proliferation, unlike in nonmuscle cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Insulin-like growth factor binding protein-3 (IGFBP-3) is known to inhibit the proliferation of various cell types, including myogenic cells.
  • This inhibition occurs through both insulin-like growth factor (IGF)-dependent and IGF-independent pathways.
  • The precise mechanism of IGF-independent proliferation suppression by IGFBP-3 is not fully understood, but in nonmuscle cells, it involves binding to the low-density lipoprotein receptor-related protein-1 (LRP-1).

Purpose of the Study:

  • To investigate the role of the LRP-1 receptor in IGFBP-3-mediated suppression of myogenic cell proliferation.
  • To determine if LRP-1 is necessary for IGFBP-3 to inhibit the proliferation of cultured L6 myogenic cells.

Main Methods:

  • Utilized receptor-associated protein, an LRP-1 antagonist, to assess its effect on recombinant porcine (rp)IGFBP-3 inhibition of L6 cell proliferation.
  • Employed small interfering RNA (siRNA) to silence LRP-1 expression in L6 cells, confirming knockdown via mRNA and Western blot analysis.
  • Compared the proliferation rates of LRP-1-silenced and mock-silenced L6 cells treated with rpIGFBP-3.

Main Results:

  • Treatment with receptor-associated protein partially blocked the inhibitory effect of rpIGFBP-3 on L6 cell proliferation, reducing inhibition by 37%.
  • LRP-1 small interfering RNA effectively reduced LRP-1 mRNA levels by over 80% and rendered the LRP-1 protein undetectable in L6 cells.
  • Despite significant LRP-1 knockdown, rpIGFBP-3 suppressed proliferation rates in LRP-1-silenced cells to the same extent as in control (mock-silenced) cells.

Conclusions:

  • The LRP-1 receptor is not required for IGFBP-3 to suppress the proliferation of L6 myogenic cells.
  • These findings contrast with data from nonmuscle cell lines, suggesting a cell-type-specific mechanism for IGFBP-3's IGF-independent actions.
  • The study highlights a divergence in the molecular pathways mediating IGFBP-3's antiproliferative effects between muscle and nonmuscle cell types.

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