SMAD3-dependent and -independent pathways in glomerular injury associated with experimental glomerulonephritis.
Am J Physiol Renal Physiol
; 317(1): F152-F162, 2019 07 01.
Article
en En
| MEDLINE
| ID: mdl-31141397
ABSTRACT
Glomerulonephritis (GN) is a common cause of end-stage kidney disease and is characterized by glomerular inflammation, hematuria, proteinuria, and progressive renal dysfunction. Transforming growth factor (TGF)-ß is involved in glomerulosclerosis and interstitial fibrosis. TGF-ß activates multiple signaling pathways, including the canonical SMAD pathway. We evaluated the role of SMAD signaling in renal injury and proteinuria in a murine model of GN. SMAD3+/+ or SMAD3-/- mice received anti-glomerular basement membrane antibodies to induce GN. We confirmed previous reports that demonstrated that SMAD3 is an important mediator of glomerulosclerosis and renal interstitial fibrosis. Proteinuria was highly SMAD3 dependent. We found differential effects of SMAD3 deletion on podocytes and glomerular endothelial cells. GN led to podocyte injury, including foot process effacement and loss of podocyte-specific markers. Interestingly, these changes were not SMAD3 dependent. Furthermore, there were significant changes to glomerular endothelial cells, including loss of fenestrations, swelling, and basement membrane reduplication, which were SMAD3 dependent. Despite ongoing markers of podocyte injury in SMAD3-/- mice, proteinuria was transient. Renal injury in the setting of GN involves TGF-ß and SMAD3 signaling. Cell populations within the glomerulus respond differently to SMAD3 deletion. Proteinuria correlated more with endothelial cell changes as opposed to podocyte injury in this model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad por Anticuerpos Antimembrana Basal Glomerular
/
Proteína smad3
/
Glomérulos Renales
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá