Ca(2+)-binding protein expression in primary human thyrocytes

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Signaling

Background:

• Calcium-binding proteins (CaBP) from S100 and annexin families are regulated by TSH in FRTL-5 cells.
• Investigating CaBP regulation in primary human thyrocytes (PHT) from different thyroid tissues is crucial for understanding thyroid physiology.

Purpose of the Study:

• To study the regulation of S100A4, S100A6, and ANXA2 in PHT.
• To investigate the effect of CaBP expression on calcium (Ca2+) and TSH receptor (TSHR) signaling.
• To explore the role of CaBP in thyroid cell proliferation and differentiation.

Main Methods:

• Assessed CaBP expression (S100A4, S100A6, ANXA2) in PHT from surrounding tissues, cold benign thyroid nodules, and autonomously functioning thyroid nodules.
• Utilized cell culture models accounting for PHT proliferation and differentiation markers (FOS, TPO).
• Investigated signaling pathways (PKA, MEK1/2, PI3-K) and triiodothyronine involvement in CaBP regulation.
• Analyzed Ca2+ signaling responses to ATP and TSH.
• Employed S100A4 mutants to study protein interaction effects.

Main Results:

• CaBP regulation strongly correlated with the proliferation marker FOS.
• PKA, MEK1/2, PI3-K, and triiodothyronine were identified as regulators of CaBP expression.
• Modulated CaBP expression altered ATP-elicited Ca2+ signaling; S100A4 affected subsequent Ca2+ responses and buffering, while ANXA2 influenced the initial Ca2+ response.
• S100A4 overexpression reduced TSH-induced NFAT activation.
• S100A4's effects on Ca2+ signaling are mediated by protein interactions.

Conclusions:

• TSH regulates CaBP expression, thereby fine-tuning Ca2+ signals in thyrocytes.
• This represents a novel cross-regulating mechanism in thyrocytes with potential implications for thyroid cell signaling and physiology.
• CaBP play distinct roles in modulating Ca2+ signaling dynamics within thyroid cells.