Dual roles of parathyroid hormone related protein in TGF-ß1 signaling and fibronectin up-regulation in mesangial cells.
Biosci Rep
; 37(5)2017 Oct 31.
Article
en En
| MEDLINE
| ID: mdl-28954822
ABSTRACT
Little is known about the cross-talk between parathyroid hormone (PTH) related protein (PTHrP) and TGF-ß1 in mesangial cells (MCs). Our results showed that PTHrP treatment (≤3 h) induced internalization of PTH1R (PTH/PTHrP receptor)-TßRII (TGF-ß type 2 receptor) complex and suppressed TGF-ß1-mediated Smad2/3 activation and fibronectin (FN) up-regulation. However, prolonged PTHrP treatment (12-48 h) failed to induce PTH1R-TßRII association and internalization. Total protein levels of PTH1R and TßRII were unaffected by PTHrP treatment. These results suggest that internalization of PTH1R and TßRII after short PTHrP treatment might not lead to their proteolytic destruction, allowing the receptors to be recycled back to the plasma membrane during prolonged PTHrP exposure. Receptor re-expression at the cell surface allows PTHrP to switch from its initial inhibitory effect to promote induction of FN. Our study thus demonstrates the dual roles of PTHrP on TGF-ß1 signaling and FN up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for diabetic kidney disease (DKD).
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibronectinas
/
Proteína Relacionada con la Hormona Paratiroidea
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Nefropatías Diabéticas
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Factor de Crecimiento Transformador beta1
Límite:
Humans
Idioma:
En
Revista:
Biosci Rep
Año:
2017
Tipo del documento:
Article