Anales de la RANM

47 A N A L E S R A N M R E V I S T A F U N D A D A E N 1 8 7 9 S U P L E M E N T O I SIMPOSIO · JÓVENES INVESTIGADORES Libro de Abstracts An RANM. 2021;138(03).supl01: 47 - 54 its expression increased in human and murine kidney fibrosis. Genetic CD74 deficiency resulted in upregulation in RNA and protein levels of fibrosis markers α-SMA, collagen, fibronectin, and downregulation of the nephroprotective gene Klotho, and in more a severe chronic kidney disease than inwild type mice. Conclusion: Our study provides evidence that CD74 has a nephroprotective role in kidney fibrosis in chromic kidney disease. Growth differentiation factor-15 (GDF15) is a member of the GDF subfamily with potential nephroprotective functions. We have now explored the role of GDF15 in the regulation of the expression of the nephroprotective factor Klotho in acute kidney injury (AKI) and kidney fibrosis in mice. GDF15 was the most upregu- lated GDF family gene in experimental nephro- toxic AKI and in kidney fibrosis transcripto- mics. The function of GDF15 was explored in nephrotoxic AKI in genetically modified mice and following the exogenous administration of recombinant GDF15. Gdf15 -deficient mice developed more severe AKI induced by either folic acid or cisplatin while GDF15 overexpres- sing mice were protected and recombinant human GDF15 administration protected from folate- induced AKI. Kidney expression of Klotho was more severely depressed in Gdf15 deficient mice and was preserved by GDF15 overexpression or rhGDF15 treatment. Kidney fibrosis induced by unilateral ureteral obstruction was also more severe in Gdf15 -deficient mice while consti- tutive GDF15 overexpression decreased kidney injury and preserved Klotho expression. In tubular cells cultured in an inflammatory milieu, GDF15 preserved Klotho expression. In conclusion, a spontaneous increased kidney expression of endogenous GDF15 is not enough to prevent kidney injury, but further increments in GDF15 are nephroprotective and preserve the kidney expression of the nephroprotective factor Klotho in acute and chronic settings. GDF15 PRESERVES KLOTHO EXPRESSION IN ACUTE KIDNEY INJURY AND KIDNEY FIBROSIS GDF15 MANTIENE LA EXPRESIÓN DE KLOTHO EN LA INSUFICIENCIA RENAL AGUDA Y LA FIBROSIS RENAL Lara Valiño-Rivas 1 , Leticia Cuarental 1 , Maria Vanessa Perez-Gomez 1 , Alberto Ortiz 1 , Maria Dolores Sanchez- Niño 1, 2 1 Department of Nephrology and Hypertension. IIS-Funda- cion Jimenez Diaz, Madrid, Spain. 2 Department of Pharmacology, Universidad Autonoma de Madrid, Spain