Basic fibroblast growth factor reduces functional and structural damage in chronic kidney disease

Villanueva, S.; Contreras, F; Tapia, A; Carreno, J.E.; Vergara C.; Ewertz, E; Cespedes, C; Irarrázabal C.; Sandoval M.; Velarde, V; Vio C.P.


Chronic kidney disease (CKD) is characterized by loss of renal function. The pathological processes involved in the progression of this condition are already known, but the molecular mechanisms have not been completely explained. Recent reports have shown the intrinsic capacity of the kidney to undergo repair after acute injury through the reexpression of repairing proteins (Villanueva S, Cespedes C, Vio CP. Am J Physiol Regul Integr Comp Physiol 290: R861-R870, 2006). Stimulation with basic fibroblast growth factor (bFGF) could accelerate this process. However, it is not known whether bFGF can induce this phenomenon in kidney cells affected by CKD. Our aim was to study the evolution of renal damage in animals with CKD treated with bFGF and to relate the amount of repairing proteins with renal damage progression. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy (NPX) and treated with bFGF (30 mu g/kg, NPX + bFGF); a control NPX group was treated with saline (NPX + S). Animals were euthanized 35 days after bFGF administration. Functional effects were assessed based on serum creatinine levels; morphological damage was assessed by the presence of macrophages (ED-1), interstitial alpha-smooth muscle actin (alpha-SMA), and interstitial collagen through Sirius red staining. The angiogenic factors VEGF and Tie-2 and the epithelial/tubular factors Ncam, bFGF, Pax-2, bone morphogenic protein-7, Noggin, Lim-1, Wnt-4, and Smads were analyzed. Renal stem cells were evaluated by Oct-4. We observed a significant reduction in serum creatinine levels, ED-1, alpha-SMA, and Sirius red as well as an important induction of Oct-4, angiogenic factors, and repairing proteins in NPX + bFGF animals compared with NPX + S animals. These results open new perspectives toward reducing damage progression in CKD.

Más información

Título según WOS: Basic fibroblast growth factor reduces functional and structural damage in chronic kidney disease
Título de la Revista: American Journal Physiology-Renal Physiology
Volumen: 306
Número: 4
Fecha de publicación: 2014
Página de inicio: F430
Página final: F441
Idioma: English


Notas: ISI