Cargando…

Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids

Hyperglycemia is a causative factor in the pathogenesis of respiratory diseases, known to induce fibrosis and inflammation in the lung. However, little attention has been paid to genes related to hyperglycemic-induced lung alterations and stem cell applications for therapeutic use. In this study, ou...

Descripción completa

Detalles Bibliográficos
Autores principales: Rasaei, Roya, Kim, Eunbi, Kim, Ji-Young, Na, Sunghun, Kim, Jung-Hyun, Heo, Jinbeom, Shin, Dong-Myung, Choi, Sun Shim, Hong, Seok-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555027/
https://www.ncbi.nlm.nih.gov/pubmed/32932992
http://dx.doi.org/10.3390/biomedicines8090346
_version_ 1783593911667654656
author Rasaei, Roya
Kim, Eunbi
Kim, Ji-Young
Na, Sunghun
Kim, Jung-Hyun
Heo, Jinbeom
Shin, Dong-Myung
Choi, Sun Shim
Hong, Seok-Ho
author_facet Rasaei, Roya
Kim, Eunbi
Kim, Ji-Young
Na, Sunghun
Kim, Jung-Hyun
Heo, Jinbeom
Shin, Dong-Myung
Choi, Sun Shim
Hong, Seok-Ho
author_sort Rasaei, Roya
collection PubMed
description Hyperglycemia is a causative factor in the pathogenesis of respiratory diseases, known to induce fibrosis and inflammation in the lung. However, little attention has been paid to genes related to hyperglycemic-induced lung alterations and stem cell applications for therapeutic use. In this study, our microarray data revealed significantly increased levels of junctional adhesion molecule 2 (JAM2) in the high glucose (HG)-induced transcriptional profile in human perivascular cells (hPVCs). The elevated level of JAM2 in HG-treated hPVCs was transcriptionally and epigenetically reversible when HG treatment was removed. We further investigated the expression of JAM2 using in vivo and in vitro hyperglycemic models. Our results showed significant upregulation of JAM2 in the lungs of streptozotocin (STZ)-induced diabetic mice, which was greatly suppressed by the administration of conditioned medium obtained from human mesenchymal stem cell cultures. Furthermore, JAM2 was found to be significantly upregulated in human pluripotent stem cell-derived multicellular alveolar organoids by exposure to HG. Our results suggest that JAM2 may play an important role in STZ-induced lung alterations and could be a potential indicator for predicting the therapeutic effects of stem cells and drugs in diabetic lung complications.
format Online
Article
Text
id pubmed-7555027
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75550272020-10-14 Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids Rasaei, Roya Kim, Eunbi Kim, Ji-Young Na, Sunghun Kim, Jung-Hyun Heo, Jinbeom Shin, Dong-Myung Choi, Sun Shim Hong, Seok-Ho Biomedicines Article Hyperglycemia is a causative factor in the pathogenesis of respiratory diseases, known to induce fibrosis and inflammation in the lung. However, little attention has been paid to genes related to hyperglycemic-induced lung alterations and stem cell applications for therapeutic use. In this study, our microarray data revealed significantly increased levels of junctional adhesion molecule 2 (JAM2) in the high glucose (HG)-induced transcriptional profile in human perivascular cells (hPVCs). The elevated level of JAM2 in HG-treated hPVCs was transcriptionally and epigenetically reversible when HG treatment was removed. We further investigated the expression of JAM2 using in vivo and in vitro hyperglycemic models. Our results showed significant upregulation of JAM2 in the lungs of streptozotocin (STZ)-induced diabetic mice, which was greatly suppressed by the administration of conditioned medium obtained from human mesenchymal stem cell cultures. Furthermore, JAM2 was found to be significantly upregulated in human pluripotent stem cell-derived multicellular alveolar organoids by exposure to HG. Our results suggest that JAM2 may play an important role in STZ-induced lung alterations and could be a potential indicator for predicting the therapeutic effects of stem cells and drugs in diabetic lung complications. MDPI 2020-09-11 /pmc/articles/PMC7555027/ /pubmed/32932992 http://dx.doi.org/10.3390/biomedicines8090346 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rasaei, Roya
Kim, Eunbi
Kim, Ji-Young
Na, Sunghun
Kim, Jung-Hyun
Heo, Jinbeom
Shin, Dong-Myung
Choi, Sun Shim
Hong, Seok-Ho
Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids
title Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids
title_full Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids
title_fullStr Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids
title_full_unstemmed Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids
title_short Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids
title_sort regulation of jam2 expression in the lungs of streptozotocin-induced diabetic mice and human pluripotent stem cell-derived alveolar organoids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555027/
https://www.ncbi.nlm.nih.gov/pubmed/32932992
http://dx.doi.org/10.3390/biomedicines8090346
work_keys_str_mv AT rasaeiroya regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT kimeunbi regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT kimjiyoung regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT nasunghun regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT kimjunghyun regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT heojinbeom regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT shindongmyung regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT choisunshim regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids
AT hongseokho regulationofjam2expressioninthelungsofstreptozotocininduceddiabeticmiceandhumanpluripotentstemcellderivedalveolarorganoids