To add new molecular and pathogenetic insights into the biological machinery associated to kidney allograft fibrosis is a major research target in nephrology and organ transplant translational medicine. Interstitial fibrosis associated to tubular atrophy (IF/TA) is, in fact, an inevitable and progressive process that occurs in almost every type of chronic allograft injury (particularly in grafts from expanded criteria donors) characterized by profound remodeling and excessive production/deposition of fibrillar extracellular matrix (ECM) with a great clinical impact. IF/TA is detectable in more than 50% of kidney allografts at 2 years. However, although well studied, the complete cellular/biological network associated with IF/TA is only partially evaluated. In the last few years, then, thanks to the introduction of new biomolecular technologies, inflammation in scarred/fibrotic parenchyma areas (recently acknowledged by the BANFF classification) has been recognized as a pivotal element able to accelerate the onset and development of the allograft chronic damage. Therefore, in this review, we focused on some new pathogenetic elements involved in graft fibrosis (including epithelial/endothelial to mesenchymal transition, oxidative stress, activation of Wnt and Hedgehog signaling pathways, fatty acids oxidation and cellular senescence) that, in our opinion, could become in future good candidates as potential biomarkers and therapeutic targets.

Kidney Allograft Fibrosis: What We Learned From Latest Translational Research Studies

Granata S;Benedetti C;Gambaro G;Zaza G.
2020-01-01

Abstract

To add new molecular and pathogenetic insights into the biological machinery associated to kidney allograft fibrosis is a major research target in nephrology and organ transplant translational medicine. Interstitial fibrosis associated to tubular atrophy (IF/TA) is, in fact, an inevitable and progressive process that occurs in almost every type of chronic allograft injury (particularly in grafts from expanded criteria donors) characterized by profound remodeling and excessive production/deposition of fibrillar extracellular matrix (ECM) with a great clinical impact. IF/TA is detectable in more than 50% of kidney allografts at 2 years. However, although well studied, the complete cellular/biological network associated with IF/TA is only partially evaluated. In the last few years, then, thanks to the introduction of new biomolecular technologies, inflammation in scarred/fibrotic parenchyma areas (recently acknowledged by the BANFF classification) has been recognized as a pivotal element able to accelerate the onset and development of the allograft chronic damage. Therefore, in this review, we focused on some new pathogenetic elements involved in graft fibrosis (including epithelial/endothelial to mesenchymal transition, oxidative stress, activation of Wnt and Hedgehog signaling pathways, fatty acids oxidation and cellular senescence) that, in our opinion, could become in future good candidates as potential biomarkers and therapeutic targets.
2020
Cellular senescence; Fatty acids oxidation; Interstitial fibrosis and tubular atrophy; Kidney fibrosis; Wnt pathway; hedgehog signaling pathways.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1019039
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