Low-density lipoprotein-related receptor protein 1 (LRP-1) is not required for insulin-like growth factor binding protein 3 (IGFBP-3) to suppress L6 myogenic cell proliferation

M. S. Pampusch, E. Kamanga-Sollo, M. R. Hathaway, M. E. White, W. R. Dayton

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Insulin-like growth factor binding protein-3 (IGFBP-3) suppresses proliferation of numerous cell types, including myogenic cells, via both insulin-like growth factor (IGF)-dependent and IGF-independent mechanisms; however, the mechanism of IGF-independent suppression of proliferation is not clearly defined. In nonmuscle cells, binding of IGFBP-3 to the low-density lipoprotein receptor-related protein-1 (LRP-1)/activated α2M receptor is reportedly required for IGFBP-3 to inhibit proliferation. These findings suggest that binding to this receptor also may be required for IGFBP-3 to suppress proliferation of cultured myogenic cells. To investigate the role of the LRP-1 receptor in suppression of myogenic cell proliferation by IGFBP-3, we have examined the effect of receptor-associated protein, an LRP-1 receptor antagonist, on recombinant porcine (rp)IGFBP-3 inhibition of L6 myogenic cell proliferation. Treatment with receptor-associated protein results in a 37% decrease (P < 0.05) in the ability of rpIGFBP-3 to inhibit L6-cell proliferation. In L6 cells subjected to LRP-1 small interfering RNA treatment for 48 h (LRP-1 silenced), LRP-1 mRNA levels were reduced by greater than 80% compared with control cultures treated with nonsense small interfering RNA (mock silenced). In addition, the 85-kDa transmembrane subunit of LRP-1 was undetectable in Western immunoblots of total protein lysates from LRP-1-silenced cells. Even though LRP-1 mRNA and protein levels were dramatically reduced in LRP-1-silenced L6 cells compared with mock-silenced controls, rpIGFPB-3 suppressed proliferation rate to the same extent in both LRP-1-silenced and mock-silenced cultures. Our results strongly suggest that, in contrast to data obtained for nonmuscle cell lines, the LRP-1 receptor is not required for IGFBP-3 to suppress proliferation of L6 myogenic cells.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalDomestic Animal Endocrinology
Issue number4
StatePublished - May 2011

Bibliographical note

Funding Information:
The authors report no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. This work was supported by National Research Initiative from the USDA Cooperative State Research, Education, and Extension Service (competitive grant 2006-35206-16663 ) and by the Minnesota Agricultural Experiment Station .

Copyright 2011 Elsevier B.V., All rights reserved.


  • Insulin-like growth factor binding protein-3
  • Low-density lipoprotein receptor-related protein-1
  • Myoblast
  • Proliferation


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