title: Basic fibroblast growth factor reduces functional and structural damage in chronic kidney disease.
abstract: 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 μg/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 α-smooth muscle actin (α-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, α-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.
authors.affiliation: Laboratorio de Fisiología Integrativa y Molecular, Universidad de los Andes, San Carlos de Apoquindo 2200, Santiago, Chile. svillanueva@uandes.cl.
authors.forename: Sandra
authors.initials: S
authors.lastname: Villanueva
authors.forename: Felipe
authors.initials: F
authors.lastname: Contreras
authors.forename: Andrés
authors.initials: A
authors.lastname: Tapia
authors.forename: Juan E
authors.initials: JE
authors.lastname: Carreño
authors.forename: Cesar
authors.initials: C
authors.lastname: Vergara
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ewertz
authors.forename: Carlos
authors.initials: C
authors.lastname: Cespedes
authors.forename: Carlos
authors.initials: C
authors.lastname: Irarrazabal
authors.forename: Mauricio
authors.initials: M
authors.lastname: Sandoval
authors.forename: Victoria
authors.initials: V
authors.lastname: Velarde
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Vio
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000627:therapeutic use*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D003404:Creatinine; D042787:Receptor, TIE-2
keywords: bFGF; chronic kidney disease; renal recovery