Insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mediate TGF-β- and myostatin-induced suppression of proliferation in porcine embryonic myogenic cell cultures

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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

We have previously shown that cultured porcine embryonic myogenic cells (PEMC) produce both insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 and secrete these proteins into their media. Exogenously added recombinant porcine (rp) IGFBP-3 and rpIGFBP-5 act via IGF-dependent and IGF-independent mechanisms to suppress proliferation of PEMC cultures. Furthermore, immunoneutralization of endogenous IGFBP-3 and IGFBP-5 in the PEMC culture medium results in increased DNA synthesis rate suggesting that endogenous IGFBP-3 and IGFBP-5 suppress PEMC proliferation. TGF-β superfamily members myostatin and TGF-β1 have also been shown to suppress proliferation of myogenic cells, and treatment of cultured PEMC with either TGF-β1 or myostatin significantly (P < 0.01) increases levels of IGFBP-3 and -5 mRNA. We have previously shown that immunoneutralization of IGFBP-3 decreases the proliferation-suppressing activity of TGF-β1 and myostatin. Here, we show that immunoneutralization of IGFBP-5 also significantly (P < 0.05) decreases the DNA synthesis-suppressing activity of these molecules. Simultaneous immunoneutralization of both IGFBP-3 and IGFBP-5 in TGF-β1 or myostatin-treated PEMC cultures restores Long-R3-IGF-I-stimulated DNA synthesis rates to 90% of the levels observed in control cultures receiving no TGF-β1 or myostatin treatment (P < 0.05). Even though immunoneutralization of IGFBP-3 and -5 increased DNA synthesis rates in TGF-β1 or myostatin-treated PEMC cultures, phosphosmad2 levels in these cultures were not affected. These findings strongly suggest that IGFBP-3 and IGFBP-5 affect processes downstream from receptor-mediated Smad phosphorylation that facilitate the ability of TGF-β and myostatin to suppress proliferation of PEMC.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalExperimental Cell Research
Volume311
Issue number1
DOIs
StatePublished - Nov 15 2005

Bibliographical note

Funding Information:
Contract Grant Sponsor: USDA National Research Initiative Competitive Grants. Program: Contract Grant Number: 00-03271. Contract Grant Sponsor: Minnesota Agricultural Experiment Station.

Keywords

  • IGFBP-3
  • IGFBP-5
  • Muscle
  • Myostatin
  • Proliferation
  • Smad
  • TGF-β

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