Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging
Abstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice w...
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Nature Publishing Group
2018-03-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-018-23338-x |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yingji Jin Yoshito Takeda Yasushi Kondo Lokesh P. Tripathi Sujin Kang Hikari Takeshita Hanako Kuhara Yohei Maeda Masayoshi Higashiguchi Kotaro Miyake Osamu Morimura Taro Koba Yoshitomo Hayama Shohei Koyama Kaori Nakanishi Takeo Iwasaki Satoshi Tetsumoto Kazuyuki Tsujino Muneyoshi Kuroyama Kota Iwahori Haruhiko Hirata Takayuki Takimoto Mayumi Suzuki Izumi Nagatomo Ken Sugimoto Yuta Fujii Hiroshi Kida Kenji Mizuguchi Mari Ito Takashi Kijima Hiromi Rakugi Eisuke Mekada Isao Tachibana Atsushi Kumanogoh |
spellingShingle |
Yingji Jin Yoshito Takeda Yasushi Kondo Lokesh P. Tripathi Sujin Kang Hikari Takeshita Hanako Kuhara Yohei Maeda Masayoshi Higashiguchi Kotaro Miyake Osamu Morimura Taro Koba Yoshitomo Hayama Shohei Koyama Kaori Nakanishi Takeo Iwasaki Satoshi Tetsumoto Kazuyuki Tsujino Muneyoshi Kuroyama Kota Iwahori Haruhiko Hirata Takayuki Takimoto Mayumi Suzuki Izumi Nagatomo Ken Sugimoto Yuta Fujii Hiroshi Kida Kenji Mizuguchi Mari Ito Takashi Kijima Hiromi Rakugi Eisuke Mekada Isao Tachibana Atsushi Kumanogoh Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging Scientific Reports |
author_facet |
Yingji Jin Yoshito Takeda Yasushi Kondo Lokesh P. Tripathi Sujin Kang Hikari Takeshita Hanako Kuhara Yohei Maeda Masayoshi Higashiguchi Kotaro Miyake Osamu Morimura Taro Koba Yoshitomo Hayama Shohei Koyama Kaori Nakanishi Takeo Iwasaki Satoshi Tetsumoto Kazuyuki Tsujino Muneyoshi Kuroyama Kota Iwahori Haruhiko Hirata Takayuki Takimoto Mayumi Suzuki Izumi Nagatomo Ken Sugimoto Yuta Fujii Hiroshi Kida Kenji Mizuguchi Mari Ito Takashi Kijima Hiromi Rakugi Eisuke Mekada Isao Tachibana Atsushi Kumanogoh |
author_sort |
Yingji Jin |
title |
Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging |
title_short |
Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging |
title_full |
Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging |
title_fullStr |
Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging |
title_full_unstemmed |
Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging |
title_sort |
double deletion of tetraspanins cd9 and cd81 in mice leads to a syndrome resembling accelerated aging |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-03-01 |
description |
Abstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence. |
url |
https://doi.org/10.1038/s41598-018-23338-x |
work_keys_str_mv |
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doaj-da2c46c81ad548f99dba428cdb8e98c62020-12-08T06:04:43ZengNature Publishing GroupScientific Reports2045-23222018-03-018111410.1038/s41598-018-23338-xDouble deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated agingYingji Jin0Yoshito Takeda1Yasushi Kondo2Lokesh P. Tripathi3Sujin Kang4Hikari Takeshita5Hanako Kuhara6Yohei Maeda7Masayoshi Higashiguchi8Kotaro Miyake9Osamu Morimura10Taro Koba11Yoshitomo Hayama12Shohei Koyama13Kaori Nakanishi14Takeo Iwasaki15Satoshi Tetsumoto16Kazuyuki Tsujino17Muneyoshi Kuroyama18Kota Iwahori19Haruhiko Hirata20Takayuki Takimoto21Mayumi Suzuki22Izumi Nagatomo23Ken Sugimoto24Yuta Fujii25Hiroshi Kida26Kenji Mizuguchi27Mari Ito28Takashi Kijima29Hiromi Rakugi30Eisuke Mekada31Isao Tachibana32Atsushi Kumanogoh33Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaSumitomo Dainippon Pharma Co., LtdNational Institute of Biomedical Innovation, Health and NutritionDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Geriatric Medicine &, Osaka University Graduate School of MedicineDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Geriatric Medicine &, Osaka University Graduate School of MedicineSumitomo Dainippon Pharma Co., LtdDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaNational Institute of Biomedical Innovation, Health and NutritionNational Institute of Biomedical Innovation, Health and NutritionDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Geriatric Medicine &, Osaka University Graduate School of MedicineDepartment of Cell Biology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, SuitaAbstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence.https://doi.org/10.1038/s41598-018-23338-x |