L- and S-endoglin differentially modulate TGFβ1 signaling mediated by ALK1 and ALK5 in L6E9 myoblasts

Soraya Velasco, Patricia Alvarez-Muñoz, Miguel Pericacho, Peter ten Dijke, Carmelo Bernabéu, José M. López-Novoa, Alicia Rodríguez-Barbero

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

TGFβ regulates cellular processes by binding to type I and type II TGFβ receptors (TβRI and TβRII, respectively). In addition to these signaling receptors, endoglin is an accessory TGFβ receptor that regulates TGFβ signaling. Although there are two different alternatively spliced isoforms of endoglin, L-endoglin (L, long) and S-endoglin (S, short), little is known about the effects of S-endoglin isoform on TGFβ signaling. Here, we have analyzed the TGFβ1 signaling pathways and the effects of L- and S-endoglin in endoglin-deficient L6E9 cells. We found that TGFβ activates two distinct TβRI-Smad signaling pathways: ALK1-Smad1-Id1 and ALK5-Smad2-PAI1, in these cells. Interestingly, L-endoglin enhanced the ALK1-Id1 pathway, while S-endoglin promoted the ALK5-PAI1 route. These effects on signaling are supported by biological effects on TGFβ1-induced collagen I expression and inhibition of cell proliferation. Thus, while L-endoglin decreased TGFβ1-induced collagen I and CTGF expression and increased TGβ1-induced proliferation, S-endoglin strongly increased TGFβ1-induced collagen I and CTGF expression, and reduced TGFβ1-induced cell proliferation.

Original languageEnglish (US)
Pages (from-to)913-919
Number of pages7
JournalJournal of cell science
Volume121
Issue number6
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

Keywords

  • ALK5
  • Collagen I
  • Id1
  • PAI1
  • Proliferation
  • S-endoglin ALK1
  • Smads
  • TGFβ-L-endoglin

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