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Abstract: PO0521

Integrated Transcriptomic and Proteomic Analyses for the Characterization of Oxyphil Cells in Patients with Uremic Secondary Hyperparathyroidism

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Author

  • Mao, Jianping, Huashan Hospital Fudan University, Shanghai, Shanghai, China
Background

Calcitriol and calcimimetics are the most powerful treatments for secondary hyperparathyroidism (SHPT); however, the mechanisms leading to calcitriol or calcimimetic resistance in oxyphil cell–predominant SHPT are unknown. Here we used transcriptomic RNA-seq and tandem mass tag (TMT) proteomic techniques to characterize oxyphil cells by comparing the differences between chief and oxyphil cell nodules of parathyroid glands in patients with uremia.

Methods

Transcriptomic and proteomic analyses were performed on chief and oxyphil cell nodules collected from uremic patients. We sought to verify the expression of differentially expressed genes (DEGs), and detect the expression of mitochondrion-associated proteins (voltage-dependent anion channel 1 (VDAC1) and mitochondrially encoded cytochrome c oxidase II (MT-CO2)), proliferation-related proteins (proliferating cell nuclear antigen (PCNA) and cyclinD1), parathyroid-specific factors (parathyroid hormone (PTH) and glial cells missing homolog 2 (GCM2)), and SHPT-regulating factors (vitamin-D receptor (VDR), calcium-sensing receptor (CaSR), and Klotho). The mitochondrion microstructure and mitochondrial DNA (mtDNA) copy number were measured to assess the mitochondrial mass. Freshly excised parathyroid tissues were incubated in vitro to detect PTH secretion levels.

Results

Compared to chief cell nodules, the most marked expression increases in oxyphil cell nodules were for proteins involved in mitochondrion-associated components and a series of metabolic processes. The mitochondria number, mtDNA content, and protein levels of VDAC1 and MT-CO2 were significantly increased in oxyphil cell nodules. Moreover, oxyphil cell nodules expressed PTH and GCM2, and exhibited lower protein levels of PCNA and Cyclin D1 but higher synthesis and secretion level of PTH. The protein expression of VDR, CaSR, and Klotho were significantly downregulated in oxyphil cell nodules.

Conclusion

Oxyphil cells characterized by enrich mitochondria in patients with uremic SHPT were parathyroid-derived and showed higher synthesis and secretion of PTH but lower expression of SHPT regulators than chief cells, which may contribute to the pathophysiology of SHPT and the treatment resistance to calcitriol and calcimimetics.

Funding

  • Government Support – Non-U.S.