Identification of Protein Changes in The Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach

Abstract

Background The thyroid gland and thyroid hormones control a multitude of homeostatic functions including the functions kidney related to fluid and electrolyte balance and formation of urine. In the present study we aimed to define changes in the urinary proteome characterizing alterations in thyroid hormone status.Methods An untargeted proteomic approach with network analysis was used to study 9 age-matched subjects with newly diagnosed overt hypothyroidism. Urine was collected from subjects pre and post L-thyroxine treatment. Proteome analysis was performed using two-dimensional difference in gel electrophoresis coupled with mass spectrometry.Results 42 proteins were found to have significant differential abundance (≥1.5-fold change, ANOVA, p ≤ 0.05). 28 proteins were upregulated and 14 proteins were downregulated in the hypothyroid compared to the euthyroid state. The differentially abundant proteins investigated by Ingenuity Pathway Analysis showed involvement of signaling pathways related to MAPK Kinase, VEGF, Pi3 Kinase/Akt, Pkc, and nvolvement of pathway related to amino acid metabolism, molecular transport, small molecule biochemistry.Conclusions The differentially abundant proteins identified revealed their involvement in regulating TH and Tg metabolism. The alterations in levels of identified proteins in indicate a compensatory increase in the regulation of Tg to increase circulating TH levels in the hypothyroid state.

Proteomics Profiling of the Urine of Patients with Hyperthyroidism after Anti-Thyroid Treatment

“…Protein S100-A9 belongs to a family of calcium-binding phagocyte-specific proteins that exhibit diverse functions and cell-specific expression patterns. It is known to exist as a heterodimer in conjunction with S100A8 (S100A8/A9 or calprotectin) that is secreted in response to inflammation [ 8 ] and has emerged as a reliable biomarker of disease activity with diagnostic, prognostic, and predictive potential [ 14 ]. Increased levels of S100A8/A9 have been observed in a multitude of inflammatory diseases, including adult SLE, systemic juvenile idiopathic arthritis, and inflammatory bowel disease, in predicting the development of chronic kidney disease and distinguishing between intrinsic and prerenal acute kidney injury [ 15 ].…”

“…These studies have undoubtedly added to our understanding of TH action, although there is still a paucity of human studies. In our previous work, we used the proteomics approach in describing the alterations of the plasma proteome in patients with hyperthyroidism and hypothyroidism before and after treatment and the urinary proteome of patients with hypothyroidism [ 6 , 7 , 8 ]. In the present study, we aimed to look at the urinary proteome of the hyperthyroid patients using a quantitative 2D-DIGE followed by matrix-assisted laser desorption and ionization time of flight (MALDI-TOF) mass spectrometry (MS) during the disease state and after six months of anti-thyroid therapy in which they reverted to a normal euthyroid state.…”