Abstract: PO0534
Linking CKD with COPD: Kidney-Lung Cross-Talk and the Role of Phosphate and FGF-23 in the Bronchial Epithelium
Session Information
- Bone and Mineral Metabolism: Causes and Consequences
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Bollenbecker, Seth, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Easter, Molly, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Barnes, Jarrod W., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Faul, Christian, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Krick, Stefanie, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Dysregulation of phosphate homeostasis and increased circulating FGF23 levels are associated with chronic kidney disease (CKD); however, their role in pulmonary pathology remains poorly defined. Hyperphosphatemia is associated with increased mortality in patients with chronic obstructive pulmonary disease (COPD). Human bronchial epithelial cells (HBECs) are key effector cells in the pathogenesis of COPD, making them essential for assessing the comorbid association of COPD with CKD. Smoking is the leading cause of COPD and dramatically accelerates kidney disease occurrence. We have previously shown that FGF23 can directly affect the COPD bronchial epithelium. With the goal of improving outcomes for patients with concomitant CKD and COPD, we aimed to study the effects of phosphate, FGF23, and cigarette smoke on HBECs and their underlying mechanisms.
Methods
HBECs were treated with 1 to 5 mM sodium phosphate, FGF23, and/or cigarette smoke extract (CSE). Expression levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8 were analyzed by RT-qPCR. Concentration of these cytokines in the conditioned media was also quantified via enzyme-linked immunosorbent assay. In addition, wild type and FGFR4 knockout (FGFR4-/-) mice were fed a high phosphate diet for a total of three months or exposed to cigarette smoke for three weeks. Lung tissue was then analyzed by western blotting and RT-qPCR.
Results
Increased phosphate concentrations induced an inflammatory response in HBECs, which was further exacerbated by the addition of CSE but attenuated by FGF23 treatment. Furthermore, mice on a high phosphate diet showed increased FGF23 and IL-6 levels in their lung. The increase in IL-6 was not observed in the FGFR4-/- mice. Subacute cigarette exposure led to an increase in IL-1β and IL-8 in total lung tissue, which was abrogated in the FGFR4-/- mice.
Conclusion
Our in vitro data suggest that CKD-associated hyperphosphatemia may increase cigarette smoke induced airway inflammation, whereas our in vivo data demonstrates a role of both phosphate and FGF23 signaling in mediating lung inflammation. In summary, our results show that in CKD, there seems to be kidney-lung crosstalk with both FGF23 and phosphate as mediators of an inflammatory airway response, which seems to be mediated by FGFR4.