Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids

Abstract Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family and it’s pro-proliferative and anti-apoptosis functions could be associated with keloid pathogenesis, and blocking of mortalin and its interaction with p53 might be a potential novel target for the treatment of...

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Autores principales:	Won Jai Lee, Hyo Min Ahn, Youjin Na, Renu Wadhwa, JinWoo Hong, Chae-Ok Yun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/825a1fcdd9f647d48ffacd933a4076f6
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spelling	oai:doaj.org-article:825a1fcdd9f647d48ffacd933a4076f62021-12-02T15:06:04ZMortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids10.1038/s41598-017-13485-y2045-2322https://doaj.org/article/825a1fcdd9f647d48ffacd933a4076f62017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13485-yhttps://doaj.org/toc/2045-2322Abstract Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family and it’s pro-proliferative and anti-apoptosis functions could be associated with keloid pathogenesis, and blocking of mortalin and its interaction with p53 might be a potential novel target for the treatment of keloid. Therefore, we generated mortalin-specific small hairpin (sh) RNAs (dE1-RGD/GFP/shMot) and introduced into keloid spheroids for examination of its apoptotic and anti-fibrotic effect. On keloid tissues, mortalin expression was higher than adjacent normal tissues and it’s protein expressions were activated keloid fibroblasts (KFs). After primary keloid spheroid were transduced with dE1-RGD/GFP/shMot for knockdown of mortalin, expression of type I, III collagen, fibronectin, and elastin was significantly reduced and transforming growth factor-β1, epidermal growth factor receptor (EGFR), Extracellular Signal-Regulated Kinases 1 and 2 (Erk 1/2), and Smad 2/3 complex protein expression were decreased. In addition, increased TUNEL activities and cytochrome C were observed. Further, for examine of mortalin and p53 interaction, we performed immunofluorescence analysis. Knockdown of mortalin relocated p53 to the cell nucleus in primary keloid spheroids by dE1-RGD/GFP/shMot transduction. These results support the utility of knockdown of mortalin to induce apoptosis and reduce ECMs expression in keloid spheroid, which may be highly beneficial in treating keloids.Won Jai LeeHyo Min AhnYoujin NaRenu WadhwaJinWoo HongChae-Ok YunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Won Jai Lee Hyo Min Ahn Youjin Na Renu Wadhwa JinWoo Hong Chae-Ok Yun Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
description	Abstract Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family and it’s pro-proliferative and anti-apoptosis functions could be associated with keloid pathogenesis, and blocking of mortalin and its interaction with p53 might be a potential novel target for the treatment of keloid. Therefore, we generated mortalin-specific small hairpin (sh) RNAs (dE1-RGD/GFP/shMot) and introduced into keloid spheroids for examination of its apoptotic and anti-fibrotic effect. On keloid tissues, mortalin expression was higher than adjacent normal tissues and it’s protein expressions were activated keloid fibroblasts (KFs). After primary keloid spheroid were transduced with dE1-RGD/GFP/shMot for knockdown of mortalin, expression of type I, III collagen, fibronectin, and elastin was significantly reduced and transforming growth factor-β1, epidermal growth factor receptor (EGFR), Extracellular Signal-Regulated Kinases 1 and 2 (Erk 1/2), and Smad 2/3 complex protein expression were decreased. In addition, increased TUNEL activities and cytochrome C were observed. Further, for examine of mortalin and p53 interaction, we performed immunofluorescence analysis. Knockdown of mortalin relocated p53 to the cell nucleus in primary keloid spheroids by dE1-RGD/GFP/shMot transduction. These results support the utility of knockdown of mortalin to induce apoptosis and reduce ECMs expression in keloid spheroid, which may be highly beneficial in treating keloids.
format	article
author	Won Jai Lee Hyo Min Ahn Youjin Na Renu Wadhwa JinWoo Hong Chae-Ok Yun
author_facet	Won Jai Lee Hyo Min Ahn Youjin Na Renu Wadhwa JinWoo Hong Chae-Ok Yun
author_sort	Won Jai Lee
title	Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
title_short	Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
title_full	Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
title_fullStr	Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
title_full_unstemmed	Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
title_sort	mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/825a1fcdd9f647d48ffacd933a4076f6
work_keys_str_mv	AT wonjailee mortalindeficiencysuppressesfibrosisandinducesapoptosisinkeloidspheroids AT hyominahn mortalindeficiencysuppressesfibrosisandinducesapoptosisinkeloidspheroids AT youjinna mortalindeficiencysuppressesfibrosisandinducesapoptosisinkeloidspheroids AT renuwadhwa mortalindeficiencysuppressesfibrosisandinducesapoptosisinkeloidspheroids AT jinwoohong mortalindeficiencysuppressesfibrosisandinducesapoptosisinkeloidspheroids AT chaeokyun mortalindeficiencysuppressesfibrosisandinducesapoptosisinkeloidspheroids
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Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids

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