RT Journal Article
T1 FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats
A1 González Fernández, Rebeca
A1 González Nicolás González, María Ángeles
A1 Morales, Manuel
A1 Ávila, Julio
A1 Lázaro Fernández, Alberto
A1 Martín Vasallo, Pablo
AB The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I.
PB MDPI
SN 2073-4409
YR 2022
FD 2022-05-09
LK https://hdl.handle.net/20.500.14352/72144
UL https://hdl.handle.net/20.500.14352/72144
LA eng
NO Unión Europea
NO Ministerio de Economía y Competitividad (España)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
NO Fundación Senefro (Nefrología)
NO Fundación Mutua de Madrid
NO Gobierno de Canarias
NO Universidad de La Laguna
NO Fundación Mapfre Guanarteme
DS Docta Complutense
RD 9 abr 2025