Lavecchia Angelo M, Mantzouratou Polyxeni, Cerullo Domenico, Locatelli Monica, Conti Sara, Tironi Matteo, Sangalli Fabio, Corna Daniela, Zoja Carlamaria, Remuzzi Giuseppe, Xinaris Christodoulos
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy.
iScience. 2023 Sep 7;26(10):107826. doi: 10.1016/j.isci.2023.107826. eCollection 2023 Oct 20.
Diabetes mellitus and alterations in thyroid hormone (TH) signaling are closely linked. Though the role of TH signaling in cell differentiation and growth is well known, it remains unclear whether its alterations contribute to the pathobiology of diabetic cells. Here, we aim to investigate whether the administration of exogenous T3 can counteract the cellular remodeling that occurs in diabetic cardiomyocytes, podocytes, and pancreatic beta cells. Treating diabetic rats with T3 prevents dedifferentiation, pathological growth, and ultrastructural alterations in podocytes and cardiomyocytes. , T3 reverses glucose-induced growth in human podocytes and cardiomyocytes, restores cardiomyocyte cytoarchitecture, and reverses pathological alterations in kidney and cardiac organoids. Finally, T3 treatment counteracts glucose-induced transdifferentiation, cell growth, and loss in pancreatic beta cells through TH receptor alpha1 activation. Our studies indicate that TH signaling activation substantially counteracts diabetes-induced pathological remodeling, and provide a potential therapeutic approach for the treatment of diabetes and its complications.
糖尿病与甲状腺激素（TH）信号传导的改变密切相关。尽管TH信号传导在细胞分化和生长中的作用已为人所知，但其改变是否促成糖尿病细胞的病理生物学仍不清楚。在这里，我们旨在研究外源性T3的给药是否可以抵消糖尿病心肌细胞、足细胞和胰腺β细胞中发生的细胞重塑。用T3治疗糖尿病大鼠可防止足细胞和心肌细胞的去分化、病理性生长和超微结构改变。此外，T3可逆转葡萄糖诱导的人足细胞和心肌细胞生长，恢复心肌细胞的细胞结构，并逆转肾脏和心脏类器官的病理改变。最后，T3治疗通过激活TH受体α1抵消葡萄糖诱导的胰腺β细胞转分化、细胞生长和丢失。我们的研究表明，TH信号传导激活可显著抵消糖尿病诱导的病理重塑，并为糖尿病及其并发症的治疗提供了一种潜在的治疗方法。
