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Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury

Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type spe...

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Autores principales: Yamada, Sachiko, Nakamura, Jin, Asada, Misako, Takase, Masayuki, Matsusaka, Taiji, Iguchi, Taku, Yamada, Ryo, Tanaka, Mari, Higashi, Atsuko Y., Okuda, Tomohiko, Asada, Nariaki, Fukatsu, Atsushi, Kawachi, Hiroshi, Graf, Daniel, Muso, Eri, Kita, Toru, Kimura, Takeshi, Pastan, Ira, Economides, Aris N., Yanagita, Motoko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934867/
https://www.ncbi.nlm.nih.gov/pubmed/24586548
http://dx.doi.org/10.1371/journal.pone.0089135
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author Yamada, Sachiko
Nakamura, Jin
Asada, Misako
Takase, Masayuki
Matsusaka, Taiji
Iguchi, Taku
Yamada, Ryo
Tanaka, Mari
Higashi, Atsuko Y.
Okuda, Tomohiko
Asada, Nariaki
Fukatsu, Atsushi
Kawachi, Hiroshi
Graf, Daniel
Muso, Eri
Kita, Toru
Kimura, Takeshi
Pastan, Ira
Economides, Aris N.
Yanagita, Motoko
author_facet Yamada, Sachiko
Nakamura, Jin
Asada, Misako
Takase, Masayuki
Matsusaka, Taiji
Iguchi, Taku
Yamada, Ryo
Tanaka, Mari
Higashi, Atsuko Y.
Okuda, Tomohiko
Asada, Nariaki
Fukatsu, Atsushi
Kawachi, Hiroshi
Graf, Daniel
Muso, Eri
Kita, Toru
Kimura, Takeshi
Pastan, Ira
Economides, Aris N.
Yanagita, Motoko
author_sort Yamada, Sachiko
collection PubMed
description Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs) and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.
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spelling pubmed-39348672014-03-04 Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury Yamada, Sachiko Nakamura, Jin Asada, Misako Takase, Masayuki Matsusaka, Taiji Iguchi, Taku Yamada, Ryo Tanaka, Mari Higashi, Atsuko Y. Okuda, Tomohiko Asada, Nariaki Fukatsu, Atsushi Kawachi, Hiroshi Graf, Daniel Muso, Eri Kita, Toru Kimura, Takeshi Pastan, Ira Economides, Aris N. Yanagita, Motoko PLoS One Research Article Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs) and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury. Public Library of Science 2014-02-25 /pmc/articles/PMC3934867/ /pubmed/24586548 http://dx.doi.org/10.1371/journal.pone.0089135 Text en © 2014 Yamada et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yamada, Sachiko
Nakamura, Jin
Asada, Misako
Takase, Masayuki
Matsusaka, Taiji
Iguchi, Taku
Yamada, Ryo
Tanaka, Mari
Higashi, Atsuko Y.
Okuda, Tomohiko
Asada, Nariaki
Fukatsu, Atsushi
Kawachi, Hiroshi
Graf, Daniel
Muso, Eri
Kita, Toru
Kimura, Takeshi
Pastan, Ira
Economides, Aris N.
Yanagita, Motoko
Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury
title Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury
title_full Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury
title_fullStr Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury
title_full_unstemmed Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury
title_short Twisted Gastrulation, a BMP Antagonist, Exacerbates Podocyte Injury
title_sort twisted gastrulation, a bmp antagonist, exacerbates podocyte injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934867/
https://www.ncbi.nlm.nih.gov/pubmed/24586548
http://dx.doi.org/10.1371/journal.pone.0089135
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