Although anti-inflammatory therapies have attenuated cystogenesis in animal models, inflammatory cells may also have reparative actions. Thus, in developing therapies for PKD, it is prudent to consider the potential negative outcomes of ablating inflammation, and whether it is more viable to target certain inflammatory pathways over others. Polycystic kidney diseases (PKD) are a group of genetically inheritable disorders that are characterized by the formation of bilateral renal cysts. Autosomal dominant PKD (ADPKD) involves
mutation of the genes Pkd1 and/or Pkd2, which encode the ciliary cystoproteins, polycystin 1 and 2 (PC1 and PC2) respectively.[2, 3] Autosomal recessive PKD (ARPKD) is characterized by genetic mutation of Pkhd1, leading to defects in the cystoprotein, fibrocystin. In both forms of PKD, dilation of renal tubules gives C59 wnt supplier rise to the cystic morphology.[5, 6] Cyst growth is propagated by cystic epithelial cell (CEC) proliferation and dedifferentiation, Carfilzomib in vitro fluid secretion and basement membrane abnormalities. This cystic expansion compresses the surrounding renal parenchyma and microvasculature, obstructing nephrons and thus impairing their function, resulting in renal failure. Although research in PKD has focussed on preventing cyst growth and expansion, another key pathological feature of cystic renal disease is the development of interstitial
inflammation and fibrosis, typically associated with inflammatory cell infiltration.[7, 10, 11] Generally speaking,
PKD is not a primary inflammatory disorder. However, for many years it has been unclear whether interstitial inflammation is merely associated with disease progression in PKD, or whether it essentially plays a role in pathogenesis. Recent studies in animal models suggest that the chronic interstitial inflammation in PKD possibly contributes to cyst development and renal impairment, but the precise roles of macrophages and other infiltrating inflammatory cells have not been defined. This review aims to analyse the potential mechanisms leading to renal interstitial inflammation in PKD, including the roles of soluble mediators, intracellular signalling pathways, and the interplay between these pathways and cystoprotein dysregulation. There is substantial heterogeneity among peripheral and tissue monocytes, in humans, as well SPTLC1 as mice. Resident monocytes are characterized by CD16+ and Ly6Clow expression in humans and mice, respectively (see Table 1). These cells ‘crawl’ across endothelial vessels, and are therefore thought to monitor surrounding cells for injury. In contrast, inflammatory monocytes display a CD16− and Ly6Chigh profile in humans and mice, respectively, and infiltrate renal tissue in inflammatory states such as ischemia reperfusion injury (IRI). Once they have migrated to the injured region, these monocytes differentiate into inflammatory macrophages.