Abstract:

Background/aim: Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angiotensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1). Materials and methods: Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also immunohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies. Results: TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analysis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05). Conclusion: In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.

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