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Thyroid Hormone Signalling Alteration in Diabetic Nephropathy and Cardiomyopathy: a “Switch” to the Foetal Gene Programme

  • Microvascular Complications—Nephropathy (B Roshanravan, Section Editor)
  • Published:
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Abstract

Purpose of the Review

In this study, we will analyse how diabetes induces the reactivation of organs’ developmental programmes and growth, discuss how thyroid hormone (TH) signalling orchestrates these processes, and suggest novel strategies for exploiting TH-mediated reparative and regenerative properties.

Recent Findings

Diabetes is a global pandemic that poses an enormous threat to human health. The kidney and the heart are among the organs that are the most severely damaged by diabetes over time. They undergo profound metabolic, structural, and functional changes that may be due (at least partially) to a recapitulation of their early developmental programmes. There is growing evidence to suggest that this foetal reprogramming is controlled by the TH/TH receptor alpha 1 (TRα1) axis.

Summary

We introduce the hypothesis that in diabetes—and probably in other diseases—TH signalling acts in an antagonistic manner: it recapitulates a foetal profile that is necessary to coordinate metabolic and structural adaptations to sustain energy preservation and growth, but in the long term the persistent changes in these pathways are detrimental.

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Acknowledgements

The authors wish to thank Giuseppe Remuzzi for constructive comments on the text and Kerstin Mierke for excellent editing work on the manuscript.

Funding

PM is recipient of fellowships from Persico s.r.l., Bergamo, Italy. AML is recipient of fellowships from Fondazione Aiuti per la Ricerca sulle Malattie Rare, Bergamo, Italy. PM, AML, and CX’s research is funded by Euronanomed (an ERA-NET grant), Associazione per la Ricerca sul Diabete Italia (ARDI).

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Author notes

  1. Polyxeni Mantzouratou and Angelo Michele Lavecchia contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87, 24126, Bergamo, Italy

    Polyxeni Mantzouratou, Angelo Michele Lavecchia, Rubina Novelli & Christodoulos Xinaris

  2. University of Nicosia Medical School, 93 Agiou Nikolaou Street, Engomi, 2408, Nicosia, Cyprus

    Christodoulos Xinaris

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  1. Polyxeni Mantzouratou
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  2. Angelo Michele Lavecchia
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  4. Christodoulos Xinaris
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Correspondence to Christodoulos Xinaris.

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This article is part of the Topical Collection on Microvascular Complications—Nephropathy

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Mantzouratou, P., Lavecchia, A.M., Novelli, R. et al. Thyroid Hormone Signalling Alteration in Diabetic Nephropathy and Cardiomyopathy: a “Switch” to the Foetal Gene Programme. Curr Diab Rep 20, 58 (2020). https://doi.org/10.1007/s11892-020-01344-6

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  • DOI: https://doi.org/10.1007/s11892-020-01344-6

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