Artículos de revistas
The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy
Fecha
2012Registro en:
KIDNEY INTERNATIONAL, NEW YORK, v. 82, n. 12, supl. 1, Part 3, pp. 1284-1296, DEC, 2012
0085-2538
10.1038/ki.2012.192
Autor
Tamouza, Houda
Chemouny, Jonathan M.
Kafkova, Leona Raskova
Berthelot, Laureline
Flamant, Martin
Demion, Marie
Mesnard, Laurent
Paubelle, Etienne
Walker, Francine
Julian, Bruce A.
Tissandie, Emilie
Tiwari, Meetu K.
Câmara, Niels Olsen Saraiva
Vrtovsnik, Francois
Benhamou, Marc
Novak, Jan
Monteiro, Renato C.
Moura, Ivan C.
Institución
Resumen
IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN. Kidney International (2012) 82, 1284-1296; doi:10.1038/ki.2012.192; published online 5 September 2012