Complement component C5a induces aberrant epigenetic modifications in renal tubular epithelial cells accelerating senescence by Wnt4/βcatenin signaling after ischemia/reperfusion injury
Giuseppe Castellano(University of Bari Aldo Moro), Rossana Franzin(University of Bari Aldo Moro), Fabio Sallustio(University of Bari Aldo Moro), Alessandra Stasi(University of Bari Aldo Moro), Barbara Banelli(Ospedale Policlinico San Martino), Massimo Romani(Ospedale Policlinico San Martino), Giuseppe De Palma(University of Bari Aldo Moro), Giuseppe Lucarelli(University of Bari Aldo Moro), Chiara Divella(University of Bari Aldo Moro), Michele Battaglia(University of Bari Aldo Moro), Antonio Crovace(University of Bari Aldo Moro), Francesco Staffieri(University of Bari Aldo Moro), Giuseppe Grandaliano(University of Foggia), Giovanni Stallone(University of Foggia), Pasquale Ditonno(University of Bari Aldo Moro), Paolo Cravedi(Icahn School of Medicine at Mount Sinai), Vincenzo Cantaluppi(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), Loreto Gesualdo(University of Bari Aldo Moro)
Cited by 90Open Access
Abstract
gene expression, consistent with SASP development. In accordance, in a swine model of renal I/R injury, we found the increased expression of Wnt4 and βcatenin correlating with SA-β Gal, p21, p16 and IL-6 positivity. Administration of Complement Inhibitor (C1-Inh), antagonized SASP by reducing SA-β Gal, p21, p16, IL-6 and abrogating Wnt4/βcatenin activation.Thus, C5a affects the DNA methylation of genes involved in tubular senescence. Targeting epigenetic programs and Complement may offer novels strategies to protect tubular cells from accelerated aging and to counteract progression to Chronic Kidney Disease.
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