Interference of the cold shock protein YB-1 and progranulin on tumor necrosis factor-alpha signalling in inflammatory renal disease

• Applicant: Privatdozent Dr. Jonathan Lindquist, Ph.D.
• Subject Area: Nephrology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 276732887

Y-box binding protein-1 (YB-1) belongs to the human cold shock protein superfamily. Its known functions relate to gene transcription and RNA translation that permit cell phenotypic changes and cell-cell communication. Evidence links YB-1 expression with cytokine synthesis in inflammatory kidney disease. Our data demonstrate a pronounced mesangial cell expression of YB-1 and even active protein secretion in models of mesangioproliferative disease, as well as an interaction of YB 1 with the anti-inflammatory protein progranulin. The current proposal aims to investigate the functional role(s) of the YB-1:progranulin interaction in inflammatory kidney disease. First we will address how YB-1 influences the anti-inflammatory activity of progranulin. Next we shall investigate whether the loss of YB-1 or progranulin alters the onset or progression of inflammatory kidney disease. Additionally, we shall test whether manipulating YB-1 levels alter the course of inflammatory kidney disease. And finally, we shall determine whether progranulin and tumor necrosis factor alpha levels are suitable markers for inflammatory kidney disease activity. The proposal addresses pivotal questions on the functional role(s) of YB-1 and progranulin in the pathogenesis of inflammatory kidney diseases and may open new avenues to diagnostic and therapeutic strategies.

• DFG Programme: Research Grants