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First published online 26 February 2008
doi: 10.1242/jcs.023283

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

¹ Instituto `Reina Sofía' de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, and Red de Investigación en Enfermedades Renales (RedinRen), Salamanca, Spain
² Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
³ Centro de Investigaciones Biológicas (CSIC), and Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain

^* Author for correspondence (e-mail: barberoa{at}usal.es)

Accepted 14 January 2008

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 TGFβ1-induced proliferation, S-endoglin strongly increased TGFβ1-induced collagen I and CTGF expression, and reduced TGFβ1-induced cell proliferation.

Key words: TGFβ, L-endoglin, S-endoglin ALK1, ALK5, Id1, PAI1, Smads, Collagen I, Proliferation