Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 48
Transforming Growth Factor-#1 Induces Cyclooxygenase-2 Gene Expression In Human
Mesangial Cells: Role of MAPK And PI3K pathways
Alicia Rodríguez-Barbero, Fernando Dorado, Atanasio Pandiella*, José M. López-
Novoa.
Instituto Reina Sofía de Investigación Nefrológica. Dpto de Fisiología y Farmacología.
*Centro de Investigaciones Biológicas. (CISC). Universidad de Salamanca. Campus
Unamuno, Edificio Departamental. Avda. Campo Charro s/n. 37007. Spain. E-mail:
barberoa@usal.es
Transforming growth factor-# (TGF-#) plays a fundamental role in the progression of renal
diseases. Mesangial cells play a major role in physiological and pathophysiological renal
processes. Accumulating evidence has suggested that eicosanoids derived from
cyclooxygenase 2 (COX-2) participate in a number of pathological processes in immunemediated
renal diseases. Mesangial cells express receptors for TGF-# and COX-2 expression
can be induced in mesangial cells. However, there are no studies on the possible role of TGF-
# on COX-2 expression in human mesangial cells (HMC). The aims of this study were to
assess whether TGF-#1 stimulates COX-2 expression in primary HMC, and to determine the
routes involved in TGF-#1-induced COX-2 expression and PGE2 synthesis. TGF-#1 induced
COX-2 promoter activity, COX-2 mRNA and protein expression in HMC. COX-2 induction
was accompanied by increased PGE2 synthesis. To establish the role that ERK1/2 and p38
MAPK as well as PI3K/Akt play in TGF-#1-dependent COX-2 expression, HMC were pretreated
with inhibitors of these pathways. Inhibition of ERK1/2 by the MEK inhibitors,
PD98059 or U0126 and inhibition of p38 MAPK activity by SB203580 notably decreased the
TGF-#1-dependent COX-2 protein induction and PGE2 synthesis in HMC. In addition, pretreatment
of HMC with the PI3K inhibitor LY294002 attenuated TGF-#1-induced COX-2
expression and PGE2 synthesis. These results demonstrate that TGF-#1 regulates COX-2
expression in HMC through the activation of ERK1/2, p38 MAPK, and PI3K. These data can
help to elucidate the molecular mechanisms underlying the regulation of COX-2 and open up
specific strategies for the treatment of glomerular disease.
- 234 -