Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway
OBJECTIVE—Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2016-08, Vol.36 (8), p.1549-1557 |
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| creator | Wu, Hongxian Cheng, Xian Wu Hu, Lina Takeshita, Kyosuke Hu, Chen Du, Qiuna Li, Xiang Zhu, Enbo Huang, Zhe Yisireyili, Maimaiti Zhao, Guangxian Piao, Limei Inoue, Aiko Jiang, Haiying Lei, Yanna Zhang, Xiaohong Liu, Shaowen Dai, Qiuyan Kuzuya, Masafumi Shi, Guo-Ping Murohara, Toyoaki |
| description | OBJECTIVE—Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice.
APPROACH AND RESULTS—Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet-derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor–induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation.
CONCLUSIONS—This is the first report detailing cross-interaction between toll-like receptor 2–mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation. |
| doi_str_mv | 10.1161/ATVBAHA.115.307110 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4961274</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1807878095</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4980-54bf10ddfc716c2e0bb6905bf096486d399a0abac2472f1375bd620fde8d3eaa3</originalsourceid><addsrcrecordid>eNp9kc-O0zAQxiMEYpeFF-CAfOSSXdtxnOSCFMKfVtuKqlv2ak1sp_WumwQ7adU3QOLGI_IkGFpWcOE0M_Lv-2asL4peEnxJCCdX5er2bTkpw5BeJjgjBD-KzklKWcx4wh-HHmdFnHJGz6Jn3t9hjBml-Gl0RrOEpwzz8-hbBcNG99606AaVcjA7MxxQ1bWD66xH0_ZudId4qS0MWqFb8HK04NBS92AcCqq5kRrtDKBgg1azJY3nWpnfdJ_k83JxjaBVaDFNrn98_V7eD1d9PHlXVhzdmHUL1rRrtAg37OHwPHrSgPX6xaleRJ8_vF9Vk3j26eO0KmexZEWO45TVDcFKNTIjXFKN65oXOK0bXHCWc5UUBWCoQVKW0YYkWVorTnGjdK4SDZBcRG-Ovv1Yb7WSOnwWrOid2YI7iA6M-PelNRux7naCFZzQjAWD1ycD130ZtR_E1niprYVWd6MXJMdZnuW4SANKj6h0nfdONw9rCBa_UhSnFMOQimOKQfTq7wMfJH9iCwA_AvvODtr5ezvutRMbDXbY_M_5J40FqzM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1807878095</pqid></control><display><type>article</type><title>Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Alma/SFX Local Collection</source><creator>Wu, Hongxian ; Cheng, Xian Wu ; Hu, Lina ; Takeshita, Kyosuke ; Hu, Chen ; Du, Qiuna ; Li, Xiang ; Zhu, Enbo ; Huang, Zhe ; Yisireyili, Maimaiti ; Zhao, Guangxian ; Piao, Limei ; Inoue, Aiko ; Jiang, Haiying ; Lei, Yanna ; Zhang, Xiaohong ; Liu, Shaowen ; Dai, Qiuyan ; Kuzuya, Masafumi ; Shi, Guo-Ping ; Murohara, Toyoaki</creator><creatorcontrib>Wu, Hongxian ; Cheng, Xian Wu ; Hu, Lina ; Takeshita, Kyosuke ; Hu, Chen ; Du, Qiuna ; Li, Xiang ; Zhu, Enbo ; Huang, Zhe ; Yisireyili, Maimaiti ; Zhao, Guangxian ; Piao, Limei ; Inoue, Aiko ; Jiang, Haiying ; Lei, Yanna ; Zhang, Xiaohong ; Liu, Shaowen ; Dai, Qiuyan ; Kuzuya, Masafumi ; Shi, Guo-Ping ; Murohara, Toyoaki</creatorcontrib><description>OBJECTIVE—Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice.
APPROACH AND RESULTS—Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet-derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor–induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation.
CONCLUSIONS—This is the first report detailing cross-interaction between toll-like receptor 2–mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.115.307110</identifier><identifier>PMID: 27365406</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Animals ; Basic Sciences ; Carotid Artery Injuries - enzymology ; Carotid Artery Injuries - genetics ; Carotid Artery Injuries - pathology ; Carotid Artery, Common - drug effects ; Carotid Artery, Common - enzymology ; Carotid Artery, Common - pathology ; Cathepsins - antagonists & inhibitors ; Cathepsins - deficiency ; Cathepsins - genetics ; Cathepsins - metabolism ; Cell Cycle Checkpoints ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; Genotype ; Histone Deacetylase 6 ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylases - genetics ; Histone Deacetylases - metabolism ; Male ; Mice, Knockout ; Muscle, Smooth, Vascular - enzymology ; Muscle, Smooth, Vascular - pathology ; Myocytes, Smooth Muscle - enzymology ; Myocytes, Smooth Muscle - pathology ; Neointima ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phenotype ; Phosphatidylinositol 3-Kinase - metabolism ; Phosphorylation ; Protease Inhibitors - pharmacology ; Proto-Oncogene Proteins c-akt - metabolism ; RNA Interference ; Signal Transduction ; Toll-Like Receptor 2 - genetics ; Toll-Like Receptor 2 - metabolism ; Transfection ; Vascular Remodeling ; Wound Healing - drug effects</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2016-08, Vol.36 (8), p.1549-1557</ispartof><rights>2016 American Heart Association, Inc.</rights><rights>2016 The Authors.</rights><rights>2016 The Authors. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4980-54bf10ddfc716c2e0bb6905bf096486d399a0abac2472f1375bd620fde8d3eaa3</citedby><cites>FETCH-LOGICAL-c4980-54bf10ddfc716c2e0bb6905bf096486d399a0abac2472f1375bd620fde8d3eaa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27365406$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Hongxian</creatorcontrib><creatorcontrib>Cheng, Xian Wu</creatorcontrib><creatorcontrib>Hu, Lina</creatorcontrib><creatorcontrib>Takeshita, Kyosuke</creatorcontrib><creatorcontrib>Hu, Chen</creatorcontrib><creatorcontrib>Du, Qiuna</creatorcontrib><creatorcontrib>Li, Xiang</creatorcontrib><creatorcontrib>Zhu, Enbo</creatorcontrib><creatorcontrib>Huang, Zhe</creatorcontrib><creatorcontrib>Yisireyili, Maimaiti</creatorcontrib><creatorcontrib>Zhao, Guangxian</creatorcontrib><creatorcontrib>Piao, Limei</creatorcontrib><creatorcontrib>Inoue, Aiko</creatorcontrib><creatorcontrib>Jiang, Haiying</creatorcontrib><creatorcontrib>Lei, Yanna</creatorcontrib><creatorcontrib>Zhang, Xiaohong</creatorcontrib><creatorcontrib>Liu, Shaowen</creatorcontrib><creatorcontrib>Dai, Qiuyan</creatorcontrib><creatorcontrib>Kuzuya, Masafumi</creatorcontrib><creatorcontrib>Shi, Guo-Ping</creatorcontrib><creatorcontrib>Murohara, Toyoaki</creatorcontrib><title>Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice.
APPROACH AND RESULTS—Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet-derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor–induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation.
CONCLUSIONS—This is the first report detailing cross-interaction between toll-like receptor 2–mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation.</description><subject>Animals</subject><subject>Basic Sciences</subject><subject>Carotid Artery Injuries - enzymology</subject><subject>Carotid Artery Injuries - genetics</subject><subject>Carotid Artery Injuries - pathology</subject><subject>Carotid Artery, Common - drug effects</subject><subject>Carotid Artery, Common - enzymology</subject><subject>Carotid Artery, Common - pathology</subject><subject>Cathepsins - antagonists & inhibitors</subject><subject>Cathepsins - deficiency</subject><subject>Cathepsins - genetics</subject><subject>Cathepsins - metabolism</subject><subject>Cell Cycle Checkpoints</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Genotype</subject><subject>Histone Deacetylase 6</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases - genetics</subject><subject>Histone Deacetylases - metabolism</subject><subject>Male</subject><subject>Mice, Knockout</subject><subject>Muscle, Smooth, Vascular - enzymology</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Myocytes, Smooth Muscle - enzymology</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Neointima</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Phenotype</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Phosphorylation</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA Interference</subject><subject>Signal Transduction</subject><subject>Toll-Like Receptor 2 - genetics</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Transfection</subject><subject>Vascular Remodeling</subject><subject>Wound Healing - drug effects</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc-O0zAQxiMEYpeFF-CAfOSSXdtxnOSCFMKfVtuKqlv2ak1sp_WumwQ7adU3QOLGI_IkGFpWcOE0M_Lv-2asL4peEnxJCCdX5er2bTkpw5BeJjgjBD-KzklKWcx4wh-HHmdFnHJGz6Jn3t9hjBml-Gl0RrOEpwzz8-hbBcNG99606AaVcjA7MxxQ1bWD66xH0_ZudId4qS0MWqFb8HK04NBS92AcCqq5kRrtDKBgg1azJY3nWpnfdJ_k83JxjaBVaDFNrn98_V7eD1d9PHlXVhzdmHUL1rRrtAg37OHwPHrSgPX6xaleRJ8_vF9Vk3j26eO0KmexZEWO45TVDcFKNTIjXFKN65oXOK0bXHCWc5UUBWCoQVKW0YYkWVorTnGjdK4SDZBcRG-Ovv1Yb7WSOnwWrOid2YI7iA6M-PelNRux7naCFZzQjAWD1ycD130ZtR_E1niprYVWd6MXJMdZnuW4SANKj6h0nfdONw9rCBa_UhSnFMOQimOKQfTq7wMfJH9iCwA_AvvODtr5ezvutRMbDXbY_M_5J40FqzM</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Wu, Hongxian</creator><creator>Cheng, Xian Wu</creator><creator>Hu, Lina</creator><creator>Takeshita, Kyosuke</creator><creator>Hu, Chen</creator><creator>Du, Qiuna</creator><creator>Li, Xiang</creator><creator>Zhu, Enbo</creator><creator>Huang, Zhe</creator><creator>Yisireyili, Maimaiti</creator><creator>Zhao, Guangxian</creator><creator>Piao, Limei</creator><creator>Inoue, Aiko</creator><creator>Jiang, Haiying</creator><creator>Lei, Yanna</creator><creator>Zhang, Xiaohong</creator><creator>Liu, Shaowen</creator><creator>Dai, Qiuyan</creator><creator>Kuzuya, Masafumi</creator><creator>Shi, Guo-Ping</creator><creator>Murohara, Toyoaki</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201608</creationdate><title>Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway</title><author>Wu, Hongxian ; Cheng, Xian Wu ; Hu, Lina ; Takeshita, Kyosuke ; Hu, Chen ; Du, Qiuna ; Li, Xiang ; Zhu, Enbo ; Huang, Zhe ; Yisireyili, Maimaiti ; Zhao, Guangxian ; Piao, Limei ; Inoue, Aiko ; Jiang, Haiying ; Lei, Yanna ; Zhang, Xiaohong ; Liu, Shaowen ; Dai, Qiuyan ; Kuzuya, Masafumi ; Shi, Guo-Ping ; Murohara, Toyoaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4980-54bf10ddfc716c2e0bb6905bf096486d399a0abac2472f1375bd620fde8d3eaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Basic Sciences</topic><topic>Carotid Artery Injuries - enzymology</topic><topic>Carotid Artery Injuries - genetics</topic><topic>Carotid Artery Injuries - pathology</topic><topic>Carotid Artery, Common - drug effects</topic><topic>Carotid Artery, Common - enzymology</topic><topic>Carotid Artery, Common - pathology</topic><topic>Cathepsins - antagonists & inhibitors</topic><topic>Cathepsins - deficiency</topic><topic>Cathepsins - genetics</topic><topic>Cathepsins - metabolism</topic><topic>Cell Cycle Checkpoints</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Disease Models, Animal</topic><topic>Genotype</topic><topic>Histone Deacetylase 6</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylases - genetics</topic><topic>Histone Deacetylases - metabolism</topic><topic>Male</topic><topic>Mice, Knockout</topic><topic>Muscle, Smooth, Vascular - enzymology</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Myocytes, Smooth Muscle - enzymology</topic><topic>Myocytes, Smooth Muscle - pathology</topic><topic>Neointima</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phenotype</topic><topic>Phosphatidylinositol 3-Kinase - metabolism</topic><topic>Phosphorylation</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA Interference</topic><topic>Signal Transduction</topic><topic>Toll-Like Receptor 2 - genetics</topic><topic>Toll-Like Receptor 2 - metabolism</topic><topic>Transfection</topic><topic>Vascular Remodeling</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Hongxian</creatorcontrib><creatorcontrib>Cheng, Xian Wu</creatorcontrib><creatorcontrib>Hu, Lina</creatorcontrib><creatorcontrib>Takeshita, Kyosuke</creatorcontrib><creatorcontrib>Hu, Chen</creatorcontrib><creatorcontrib>Du, Qiuna</creatorcontrib><creatorcontrib>Li, Xiang</creatorcontrib><creatorcontrib>Zhu, Enbo</creatorcontrib><creatorcontrib>Huang, Zhe</creatorcontrib><creatorcontrib>Yisireyili, Maimaiti</creatorcontrib><creatorcontrib>Zhao, Guangxian</creatorcontrib><creatorcontrib>Piao, Limei</creatorcontrib><creatorcontrib>Inoue, Aiko</creatorcontrib><creatorcontrib>Jiang, Haiying</creatorcontrib><creatorcontrib>Lei, Yanna</creatorcontrib><creatorcontrib>Zhang, Xiaohong</creatorcontrib><creatorcontrib>Liu, Shaowen</creatorcontrib><creatorcontrib>Dai, Qiuyan</creatorcontrib><creatorcontrib>Kuzuya, Masafumi</creatorcontrib><creatorcontrib>Shi, Guo-Ping</creatorcontrib><creatorcontrib>Murohara, Toyoaki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Hongxian</au><au>Cheng, Xian Wu</au><au>Hu, Lina</au><au>Takeshita, Kyosuke</au><au>Hu, Chen</au><au>Du, Qiuna</au><au>Li, Xiang</au><au>Zhu, Enbo</au><au>Huang, Zhe</au><au>Yisireyili, Maimaiti</au><au>Zhao, Guangxian</au><au>Piao, Limei</au><au>Inoue, Aiko</au><au>Jiang, Haiying</au><au>Lei, Yanna</au><au>Zhang, Xiaohong</au><au>Liu, Shaowen</au><au>Dai, Qiuyan</au><au>Kuzuya, Masafumi</au><au>Shi, Guo-Ping</au><au>Murohara, Toyoaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2016-08</date><risdate>2016</risdate><volume>36</volume><issue>8</issue><spage>1549</spage><epage>1557</epage><pages>1549-1557</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>OBJECTIVE—Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice.
APPROACH AND RESULTS—Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet-derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor–induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation.
CONCLUSIONS—This is the first report detailing cross-interaction between toll-like receptor 2–mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>27365406</pmid><doi>10.1161/ATVBAHA.115.307110</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1079-5642 |
| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2016-08, Vol.36 (8), p.1549-1557 |
| issn | 1079-5642 1524-4636 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4961274 |
| source | MEDLINE; Journals@Ovid Complete; Alma/SFX Local Collection |
| subjects | Animals Basic Sciences Carotid Artery Injuries - enzymology Carotid Artery Injuries - genetics Carotid Artery Injuries - pathology Carotid Artery, Common - drug effects Carotid Artery, Common - enzymology Carotid Artery, Common - pathology Cathepsins - antagonists & inhibitors Cathepsins - deficiency Cathepsins - genetics Cathepsins - metabolism Cell Cycle Checkpoints Cell Movement Cell Proliferation Cells, Cultured Disease Models, Animal Genotype Histone Deacetylase 6 Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases - genetics Histone Deacetylases - metabolism Male Mice, Knockout Muscle, Smooth, Vascular - enzymology Muscle, Smooth, Vascular - pathology Myocytes, Smooth Muscle - enzymology Myocytes, Smooth Muscle - pathology Neointima p38 Mitogen-Activated Protein Kinases - metabolism Phenotype Phosphatidylinositol 3-Kinase - metabolism Phosphorylation Protease Inhibitors - pharmacology Proto-Oncogene Proteins c-akt - metabolism RNA Interference Signal Transduction Toll-Like Receptor 2 - genetics Toll-Like Receptor 2 - metabolism Transfection Vascular Remodeling Wound Healing - drug effects |
| title | Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T00%3A53%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cathepsin%20S%20Activity%20Controls%20Injury-Related%20Vascular%20Repair%20in%20Mice%20via%20the%20TLR2-Mediated%20p38MAPK%20and%20PI3K%E2%88%92Akt/p-HDAC6%20Signaling%20Pathway&rft.jtitle=Arteriosclerosis,%20thrombosis,%20and%20vascular%20biology&rft.au=Wu,%20Hongxian&rft.date=2016-08&rft.volume=36&rft.issue=8&rft.spage=1549&rft.epage=1557&rft.pages=1549-1557&rft.issn=1079-5642&rft.eissn=1524-4636&rft_id=info:doi/10.1161/ATVBAHA.115.307110&rft_dat=%3Cproquest_pubme%3E1807878095%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1807878095&rft_id=info:pmid/27365406&rfr_iscdi=true |