Thyroid hormone treatment counteracts cellular phenotypical remodeling in diabetic organs.

Autor:	Lavecchia AM; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Mantzouratou P; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Cerullo D; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Locatelli M; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Conti S; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Tironi M; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Sangalli F; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Corna D; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Zoja C; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Remuzzi G; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy., Xinaris C; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87 -, 24126 Bergamo, Italy.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Sep 07; Vol. 26 (10), pp. 107826. Date of Electronic Publication: 2023 Sep 07 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.107826
Abstrakt:	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. In vitro , 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. Competing Interests: A.M.L. and C.X. are inventors of a filled patent relating to the development of thyroid hormone-nanocarriers for the treatment of diabetic cardiomyopathy and diabetic nephropathy. (© 2023 The Author(s).)
Databáze:	MEDLINE
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