Role of Fibroblast Growth Factor 23 and Klotho Crosstalk in Idiopathic Pulmonary Fibrosis.

In this study, Kl levels were assessed in human plasma and primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF-FB) and in lung tissue from mice exposed to bleomycin, which showed significant downregulation when compared to controls. Conversely, transgenic mice overexpressing KL were protected against bleomycin-induced lung fibrosis. Treatment of human lung fibroblasts with recombinant KL alone was not sufficient to inhibit TGF-b-induced collagen deposition and inflammatory marker expression. Interestingly, Fibroblast Growth Factor (FGF)23, a pro-inflammatory circulating protein for which KL is a co-receptor, was upregulated in IPF and bleomycin lungs. To our surprise, FGF23 and KL co-administration led to a significant reduction in fibrosis and inflammation in IPF-FB; FGF23 administration alone or in combination with KL stimulated KL upregulation. We conclude that in IPF, downregulation of KL may contribute to fibrosis and inflammation and FGF23 may act as a compensatory anti-fibrotic and anti-inflammatory mediator via inhibition of TGF-β signaling. Upon restoration of KL levels, the combination of FGF23 and KL leads to resolution of inflammation and fibrosis. Altogether, these data provide novel insight into the FGF23/ KL axis and its anti-fibrotic/anti-inflammatory properties, which opens new avenues for potential therapies in aging-related diseases like IPF. PMID: 31042083 [PubMed - as supplied by publisher]
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research