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An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures

Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regen...

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Autores principales: Jiang, Shumeng, Alisafaei, Farid, Huang, Yin-Yuan, Hong, Yuan, Peng, Xiangjun, Qu, Chengqing, Puapatanakul, Pongpratch, Jain, Sanjay, Miner, Jeffrey H., Genin, Guy M., Suleiman, Hani Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9432837/
https://www.ncbi.nlm.nih.gov/pubmed/36044576
http://dx.doi.org/10.1126/sciadv.abn6027
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author Jiang, Shumeng
Alisafaei, Farid
Huang, Yin-Yuan
Hong, Yuan
Peng, Xiangjun
Qu, Chengqing
Puapatanakul, Pongpratch
Jain, Sanjay
Miner, Jeffrey H.
Genin, Guy M.
Suleiman, Hani Y.
author_facet Jiang, Shumeng
Alisafaei, Farid
Huang, Yin-Yuan
Hong, Yuan
Peng, Xiangjun
Qu, Chengqing
Puapatanakul, Pongpratch
Jain, Sanjay
Miner, Jeffrey H.
Genin, Guy M.
Suleiman, Hani Y.
author_sort Jiang, Shumeng
collection PubMed
description Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regenerate foot processes of the filtration apparatus following injury. Recently identified sarcomere-like structures (SLSs) with periodically spaced myosin IIA and synaptopodin appear in injured podocytes in vivo. We hypothesized that SLSs template synaptopodin in the initial stages of recovery in response to microenvironmental stimuli and tested this hypothesis by developing an ex vivo culture system that allows control of the podocyte microenvironment. Results supported our hypothesis. SLSs in podocytes that migrated from isolated kidney glomeruli presented periodic synaptopodin-positive clusters that nucleated peripheral, foot process–like extensions. SLSs were mechanoresponsive to actomyosin inhibitors and substrate stiffness. Results suggest SLSs as mechanobiological mediators of podocyte recovery and as potential targets for therapeutic intervention.
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spelling pubmed-94328372022-09-13 An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures Jiang, Shumeng Alisafaei, Farid Huang, Yin-Yuan Hong, Yuan Peng, Xiangjun Qu, Chengqing Puapatanakul, Pongpratch Jain, Sanjay Miner, Jeffrey H. Genin, Guy M. Suleiman, Hani Y. Sci Adv Biomedicine and Life Sciences Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regenerate foot processes of the filtration apparatus following injury. Recently identified sarcomere-like structures (SLSs) with periodically spaced myosin IIA and synaptopodin appear in injured podocytes in vivo. We hypothesized that SLSs template synaptopodin in the initial stages of recovery in response to microenvironmental stimuli and tested this hypothesis by developing an ex vivo culture system that allows control of the podocyte microenvironment. Results supported our hypothesis. SLSs in podocytes that migrated from isolated kidney glomeruli presented periodic synaptopodin-positive clusters that nucleated peripheral, foot process–like extensions. SLSs were mechanoresponsive to actomyosin inhibitors and substrate stiffness. Results suggest SLSs as mechanobiological mediators of podocyte recovery and as potential targets for therapeutic intervention. American Association for the Advancement of Science 2022-08-31 /pmc/articles/PMC9432837/ /pubmed/36044576 http://dx.doi.org/10.1126/sciadv.abn6027 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Jiang, Shumeng
Alisafaei, Farid
Huang, Yin-Yuan
Hong, Yuan
Peng, Xiangjun
Qu, Chengqing
Puapatanakul, Pongpratch
Jain, Sanjay
Miner, Jeffrey H.
Genin, Guy M.
Suleiman, Hani Y.
An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
title An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
title_full An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
title_fullStr An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
title_full_unstemmed An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
title_short An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
title_sort ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9432837/
https://www.ncbi.nlm.nih.gov/pubmed/36044576
http://dx.doi.org/10.1126/sciadv.abn6027
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