L- and S-endoglin differentially modulate TGFbeta1 signaling mediated by ALK1 and ALK5 in L6E9 myoblasts.
TGFbeta regulates cellular processes by binding to type I and type II TGFbeta receptors (TbetaRI and TbetaRII, respectively). In addition to these signaling receptors, endoglin is an accessory TGFbeta receptor that regulates TGFbeta 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 TGFbeta signaling. Here, we have analyzed the TGFbeta1 signaling pathways and the effects of L- and S-endoglin in endoglin-deficient L6E9 cells. We found that TGFbeta activates two distinct TbetaRI-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 TGFbeta1-induced collagen I expression and inhibition of cell proliferation. Thus, while L-endoglin decreased TGFbeta1-induced collagen I and CTGF expression and increased TGFbeta1-induced proliferation, S-endoglin strongly increased TGFbeta1-induced collagen I and CTGF expression, and reduced TGFbeta1-induced cell proliferation.
Velasco
Soraya
S
Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, and Red de Investigación en Enfermedades Renales (RedinRen), Salamanca, Spain.
Alvarez-Muñoz
Patricia
P
Pericacho
Miguel
M
Dijke
Peter Ten
PT
Bernabéu
Carmelo
C
López-Novoa
José M
JM
Rodríguez-Barbero
Alicia
A
D029404:Activin Receptors / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D000071063:Endoglin; D006801:Humans; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
C526764:Acvrl1 protein, rat; D015703:Antigens, CD; D024042:Collagen Type I; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625843:Tgfbr1 protein, rat