Expression of a thyroglobulin (Tg) variant in mouse kidney glomerulus

Area of Science:

• Endocrinology
• Molecular Biology
• Nephrology

Background:

• Thyroglobulin (Tg) is crucial for thyroid hormone synthesis and is primarily produced by thyroid follicular cells.
• Previous studies identified a Tg mRNA fragment in mouse mesangial cells, suggesting a potential extra-thyroidal role.

Purpose of the Study:

• To investigate the transcription and translation of a unique Tg variant in the kidney.
• To characterize the novel kidney-specific Tg protein (kTg) and its potential roles.

Main Methods:

• Cloning of kTg from mouse kidney cDNA library.
• Western blot analysis using anti-Tg antibodies.
• Immunohistochemistry on kidney tissue.
• Detection of homologous transcript in human kidney.
• Analysis of patient sera (Hashimoto's thyroiditis).

Main Results:

• A unique Tg transcript (kTg) is transcribed and translated in the kidney, distinct from thyroidal Tg.
• kTg is a 40 kDa protein, initiated within intron 41 of the Tg gene, with a unique N-terminal signal peptide and identical C-terminus to thyroid Tg.
• Immunohistochemistry localized kTg to podocytes and mesangial areas of the renal glomerulus.
• A homologous transcript was found in human kidneys, and kTg was recognized by sera from Hashimoto's patients.

Conclusions:

• A novel, low molecular weight variant of thyroglobulin (kTg) is expressed in the kidney.
• This kidney-specific Tg may have physiological and pathological functions within the kidney.
• kTg serves as a potential autoantigen, implicated in autoimmune conditions like Hashimoto's thyroiditis.