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Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease
Autophagy is involved in the development of diabetic kidney disease (DKD), the leading cause of end-stage renal disease. The Fyn tyrosine kinase (Fyn) suppresses autophagy in the muscle. However, its role in kidney autophagic processes is unclear. Here, we examined the role of Fyn kinase in autophag...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136856/ https://www.ncbi.nlm.nih.gov/pubmed/37190106 http://dx.doi.org/10.3390/cells12081197 |
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author | Uehara, Ryota Yamada, Eijiro Okada, Shuichi Bastie, Claire C. Maeshima, Akito Ikeuchi, Hidekazu Horiguchi, Kazuhiko Yamada, Masanobu |
author_facet | Uehara, Ryota Yamada, Eijiro Okada, Shuichi Bastie, Claire C. Maeshima, Akito Ikeuchi, Hidekazu Horiguchi, Kazuhiko Yamada, Masanobu |
author_sort | Uehara, Ryota |
collection | PubMed |
description | Autophagy is involved in the development of diabetic kidney disease (DKD), the leading cause of end-stage renal disease. The Fyn tyrosine kinase (Fyn) suppresses autophagy in the muscle. However, its role in kidney autophagic processes is unclear. Here, we examined the role of Fyn kinase in autophagy in proximal renal tubules both in vivo and in vitro. Phospho-proteomic analysis revealed that transglutaminase 2 (Tgm2), a protein involved in the degradation of p53 in the autophagosome, is phosphorylated on tyrosine 369 (Y369) by Fyn. Interestingly, we found that Fyn-dependent phosphorylation of Tgm2 regulates autophagy in proximal renal tubules in vitro, and that p53 expression is decreased upon autophagy in Tgm2-knockdown proximal renal tubule cell models. Using streptozocin (STZ)-induced hyperglycemic mice, we confirmed that Fyn regulated autophagy and mediated p53 expression via Tgm2. Taken together, these data provide a molecular basis for the role of the Fyn–Tgm2–p53 axis in the development of DKD. |
format | Online Article Text |
id | pubmed-10136856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101368562023-04-28 Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease Uehara, Ryota Yamada, Eijiro Okada, Shuichi Bastie, Claire C. Maeshima, Akito Ikeuchi, Hidekazu Horiguchi, Kazuhiko Yamada, Masanobu Cells Article Autophagy is involved in the development of diabetic kidney disease (DKD), the leading cause of end-stage renal disease. The Fyn tyrosine kinase (Fyn) suppresses autophagy in the muscle. However, its role in kidney autophagic processes is unclear. Here, we examined the role of Fyn kinase in autophagy in proximal renal tubules both in vivo and in vitro. Phospho-proteomic analysis revealed that transglutaminase 2 (Tgm2), a protein involved in the degradation of p53 in the autophagosome, is phosphorylated on tyrosine 369 (Y369) by Fyn. Interestingly, we found that Fyn-dependent phosphorylation of Tgm2 regulates autophagy in proximal renal tubules in vitro, and that p53 expression is decreased upon autophagy in Tgm2-knockdown proximal renal tubule cell models. Using streptozocin (STZ)-induced hyperglycemic mice, we confirmed that Fyn regulated autophagy and mediated p53 expression via Tgm2. Taken together, these data provide a molecular basis for the role of the Fyn–Tgm2–p53 axis in the development of DKD. MDPI 2023-04-20 /pmc/articles/PMC10136856/ /pubmed/37190106 http://dx.doi.org/10.3390/cells12081197 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Uehara, Ryota Yamada, Eijiro Okada, Shuichi Bastie, Claire C. Maeshima, Akito Ikeuchi, Hidekazu Horiguchi, Kazuhiko Yamada, Masanobu Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease |
title | Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease |
title_full | Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease |
title_fullStr | Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease |
title_full_unstemmed | Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease |
title_short | Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease |
title_sort | fyn phosphorylates transglutaminase 2 (tgm2) and modulates autophagy and p53 expression in the development of diabetic kidney disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136856/ https://www.ncbi.nlm.nih.gov/pubmed/37190106 http://dx.doi.org/10.3390/cells12081197 |
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