As a consequence, CKD has become not only a global health issue, but also an economic problem, affecting individuals, families and societies. Renal fibrosis is considered as the hallmark of chronic kidney disease (CKD), and epidemiological studies have shown that the prevalence of patients with progressive renal failure is increasing worldwide. In conclusion, PAFR signaling contributes to a pro-inflammatory environment in the model of obstructive nephropathy, favoring the fibrotic process, which lately will generate renal dysfunction and progressive organ failure.
Also, early blockade of PAFR after UUO leads to a protective effect, with less fibrosis deposition. These indicate that PAFR engagement by PAF or PAF-like molecules generated during UUO potentiates renal dysfunction and fibrosis and might promote epithelial-to-mesenchymal transition (EMT). PAFR KO animals compared with WT mice present: (a) less renal dysfunction, evaluated by urine protein/creatinine ratio (b) less fibrosis evaluated by collagen deposition, type I collagen, Lysyl Oxidase-1 (LOX-1) and transforming growth factor β (TGF- β) gene expression, and higher expression of bone morphogenetic protein 7 (BMP-7) (3.3-fold lower TGF- β/BMP-7 ratio) (c) downregulation of extracellular matrix (ECM) and adhesion molecule-related machinery genes and (d) lower levels of pro-inflammatory cytokines. Wild-type (WT) and PAFR knockout (KO) mice underwent unilateral ureter obstruction (UUO), and at kill time, urine and kidney tissue was collected. In the present study, we investigated the role of PAF receptor (PAFR) in an experimental model of chronic renal disease. Although there is evidence of its involvement in acute renal dysfunction, its role in progressive kidney injury is not completely known. Platelet-activating factor (PAF) is a lipid mediator with important pro-inflammatory effects, being synthesized by several cell types including kidney cells.
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