Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder marked by relentless fibrosis and damage of the lung architecture. A growing body of evidence now suggests that IPF progresses as a result of aberrant epithelial-fibroblast crosstalk. Injured epithelia are a major source of growth factors such as PDGF which guide resident fibroblasts to injury sites.

Pkd2 mesenteric vessels exhibit a primary defect in endothelium-dependent vasodilatation restored by rosiglitazone.

Patients with autosomal dominant polycystic kidney disease have a high prevalence of hypertension and structural vascular abnormalities, such as intracranial aneurysms. Hypertension can develop in childhood and often precedes a significant reduction in the glomerular filtration rate. The major aim of this study was to investigate whether a primary endothelial defect or a vascular smooth muscle (VSM) defect was present in murine polycystic kidney disease (Pkd)2 heterozygous mesenteric vessels before the development of renal failure or hypertension.

Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury.

Autosomal dominant polycystic kidney disease (ADPKD) results from mutations in either PKD1 or PKD2 and accounts for 10% of all patients on renal replacement therapy. The kidney disease phenotype is primarily characterized by cyst formation, but there are also prominent interstitial changes (inflammation, apoptosis, proliferation, and fibrosis). Using a model of unilateral ischemia-reperfusion injury, we tested the hypothesis that Pkd2 heterozygous kidneys are more sensitive to injury and that this could lead to interstitial inflammation and fibrosis.