RT Journal Article
T1 TNF-related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras-dependent proliferation of cultured renal fibroblast
A1 Ucero Herrería, Álvaro Conrado
A1 Benito Martín, Alberto
A1 Fuentes Calvo, Isabel
A1 Santamaria, Beatriz
A1 Blanco González, Julia
A1 López Novoa, José M.
A1 Ruíz Ortega, Marta
A1 Egido, Jesus
A1 Burkly, Linda C.
A1 Martínez Salgado, Carlos
A1 Ortiz, Alberto
AB Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) regulates apoptosis, proliferation and inflammation in renal epithelial cells and plays a role in acute kidney injury. However, there is little information on the chronic effects of TWEAK. We hypothesized that TWEAK may influence renal fibrosis and regulate kidney fibroblast biology, in part, through Ras pathway. We studied a chronic model of experimental unilateral ureteral obstruction in wild type and TWEAK deficient mice, and a murine model of systemic TWEAK overexpression. TWEAK actions were also explored in cultured renal and embryonic fibroblasts. TWEAK and TWEAK receptor expression was increased in the obstructed kidneys. The absence of TWEAK decreased early kidney tubular damage, inflammatory infiltrates and myofibroblast number. TWEAK deficient mice had decreased renal fibrosis 21days after obstruction, as assessed by extracellular matrix staining. In mice without prior underlying kidney disease, systemic overexpression of TWEAK induced kidney inflammation and fibrosis. In cultured fibroblasts, TWEAK induced proliferation through activation of the Ras/ERK pathway. TWEAK also activated nuclear factor κB (NFκB)-dependent inflammatory chemokine production in murine renal fibroblasts. In conclusion, lack of TWEAK reduces renal fibrosis in a model of persistent kidney insult and overexpression of TWEAK led to renal fibrosis. TWEAK actions on renal fibroblasts may contribute to the in vivo observations, as TWEAK promotes inflammatory activity and proliferation in fibroblast cultures.
PB Elsevier
SN 0925-4439
YR 2013
FD 2013-06-06
LK https://hdl.handle.net/20.500.14352/116737
UL https://hdl.handle.net/20.500.14352/116737
LA eng
NO Ucero AC, Benito-Martin A, Fuentes-Calvo I, Santamaria B, Blanco J, Lopez- Novoa JM, Ruiz-Ortega M, Egido J, Burkly LC, Martinez-Salgado C, Ortiz A. TNF- related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras- dependent proliferation of cultured renal fibroblast. Biochim Biophys Acta. 2013 Oct;1832(10):1744-55
NO Fondos FEDER
NO European Commission
NO Instituto de Salud Carlos III (España)
NO Sociedad Española de Nefrologia
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 6 abr 2025