Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis
A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory...
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| Veröffentlicht in: | PloS one 2015-08, Vol.10 (8), p.e0133055-e0133055 |
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| creator | Yu, Na Zhang, Zhang Chen, Pei Zhong, Yimin Cai, Xiaoxiao Hu, Huan Yang, Ying Zhang, Jing Li, Kaijing Ge, Jian Yu, Keming Liu, Xing Zhuang, Jing |
| description | A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells.
CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2.
Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression. |
| doi_str_mv | 10.1371/journal.pone.0133055 |
| format | Article |
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CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2.
Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0133055</identifier><identifier>PMID: 26275042</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Adolescent ; Adult ; Apoptosis ; Blotting, Western ; Bone morphogenetic proteins ; Cancer ; Cell Cycle - drug effects ; Cell migration ; Cell Movement - drug effects ; Cell Survival - drug effects ; Cells, Cultured ; Chemokine CXCL12 - genetics ; Chemokine CXCL12 - metabolism ; Chemokines ; CXCR4 protein ; Cytokines ; Degeneration ; Dexamethasone ; Drugs, Chinese Herbal - chemistry ; Extracellular matrix ; Female ; Glaucoma ; Glioma cells ; Gliomas ; Glucocorticoids ; Herbal medicine ; Humans ; Hypertension ; Immunohistochemistry ; Laboratories ; Male ; Medicine ; Middle Aged ; Morphology ; Neovascularization ; Ophthalmology ; Patients ; Pharmacology ; Physiological aspects ; Polymerase chain reaction ; Prognosis ; Pulmonary fibrosis ; Pyrazines - chemistry ; Pyrazines - pharmacology ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR4 - genetics ; Receptors, CXCR4 - metabolism ; SDF-1 protein ; Surgery ; Trabecular Meshwork - drug effects ; Trabecular Meshwork - metabolism ; Trabecular Meshwork - pathology ; Traditional Chinese medicine ; Transforming growth factor-b1 ; Transforming growth factors ; Vascularization ; Young Adult</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0133055-e0133055</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Yu et al 2015 Yu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-4b748fb3d5ab9c7cc314d96b1d8278296a81bea7aec68b9f7f305ceb141035fd3</citedby><cites>FETCH-LOGICAL-c758t-4b748fb3d5ab9c7cc314d96b1d8278296a81bea7aec68b9f7f305ceb141035fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537220/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537220/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26275042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Yuan, Fan</contributor><creatorcontrib>Yu, Na</creatorcontrib><creatorcontrib>Zhang, Zhang</creatorcontrib><creatorcontrib>Chen, Pei</creatorcontrib><creatorcontrib>Zhong, Yimin</creatorcontrib><creatorcontrib>Cai, Xiaoxiao</creatorcontrib><creatorcontrib>Hu, Huan</creatorcontrib><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Li, Kaijing</creatorcontrib><creatorcontrib>Ge, Jian</creatorcontrib><creatorcontrib>Yu, Keming</creatorcontrib><creatorcontrib>Liu, Xing</creatorcontrib><creatorcontrib>Zhuang, Jing</creatorcontrib><title>Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells.
CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2.
Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression.</description><subject>Accumulation</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>Bone morphogenetic proteins</subject><subject>Cancer</subject><subject>Cell Cycle - drug effects</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Chemokine CXCL12 - genetics</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Chemokines</subject><subject>CXCR4 protein</subject><subject>Cytokines</subject><subject>Degeneration</subject><subject>Dexamethasone</subject><subject>Drugs, Chinese Herbal - chemistry</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Glaucoma</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Glucocorticoids</subject><subject>Herbal medicine</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Immunohistochemistry</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Morphology</subject><subject>Neovascularization</subject><subject>Ophthalmology</subject><subject>Patients</subject><subject>Pharmacology</subject><subject>Physiological aspects</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Pulmonary fibrosis</subject><subject>Pyrazines - chemistry</subject><subject>Pyrazines - pharmacology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, CXCR4 - genetics</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>SDF-1 protein</subject><subject>Surgery</subject><subject>Trabecular Meshwork - drug effects</subject><subject>Trabecular Meshwork - metabolism</subject><subject>Trabecular Meshwork - pathology</subject><subject>Traditional Chinese medicine</subject><subject>Transforming growth factor-b1</subject><subject>Transforming growth factors</subject><subject>Vascularization</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9Fu0zAUhiMEYmPwBggsIaFNWjs7TuLkBqnqGKu0aWgriDvLcY6TjNQutjM2noZHxaHd1KJdoFw4Ov7-_8i_faLoNcFjQhk5uja91aIbL42GMSaU4jR9Eu2SgsajLMb06cb_TvTCuWuMU5pn2fNoJ85iluIk3o1-z8FbsQDf3HXLOyt-tRrQ_vz888EhEhpNpG9vAM10baFqQXtkFJo2AXKATsGW6DzU5SCaNr3Qt63R9SGaeA-6Fx4c8g2gY6hBgxU-7A4GcytKkH0nbJC75qex3wNnTV836Or4ZESOpt-mlwma3LbuZfRMic7Bq_W6F305-Tifno7OLj7NppOzkWRp7kdJyZJclbRKRVlIJiUlSVVkJanymOVxkYmclCCYAJnlZaGYCnlJKElCME1VRfeityvfZWccX4freIwTmuVJiDcQsxVRGXHNl7ZdCHvHjWj534KxNRfWt7IDHjoqqnAZnJOEMppLXACmoFKAkgkVvD6su_XlAioZkrWi2zLd3tFtw2tzw5OUsjjc6F60vzaw5kcPzvNF6yR0ndBgescJwykmOM8H9N0_6OOnW1O1CAdotTKhrxxM-SSJ05zFpMgCNX6ECl8Fi1aGl6jaUN8SHGwJAuPh1teid47Pri7_n734us2-32AbEJ1vnOn64Ym5bTBZgdIa5yyoh5AJ5sMg3afBh0Hi60EKsjebF_Qgup8c-gfd9RkZ</recordid><startdate>20150814</startdate><enddate>20150814</enddate><creator>Yu, Na</creator><creator>Zhang, Zhang</creator><creator>Chen, Pei</creator><creator>Zhong, Yimin</creator><creator>Cai, Xiaoxiao</creator><creator>Hu, Huan</creator><creator>Yang, Ying</creator><creator>Zhang, Jing</creator><creator>Li, Kaijing</creator><creator>Ge, Jian</creator><creator>Yu, Keming</creator><creator>Liu, Xing</creator><creator>Zhuang, Jing</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150814</creationdate><title>Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis</title><author>Yu, Na ; Zhang, Zhang ; Chen, Pei ; Zhong, Yimin ; Cai, Xiaoxiao ; Hu, Huan ; Yang, Ying ; Zhang, Jing ; Li, Kaijing ; Ge, Jian ; Yu, Keming ; Liu, Xing ; Zhuang, Jing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-4b748fb3d5ab9c7cc314d96b1d8278296a81bea7aec68b9f7f305ceb141035fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Accumulation</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>Bone morphogenetic proteins</topic><topic>Cancer</topic><topic>Cell Cycle - 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chemistry</topic><topic>Pyrazines - pharmacology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, CXCR4 - genetics</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>SDF-1 protein</topic><topic>Surgery</topic><topic>Trabecular Meshwork - drug effects</topic><topic>Trabecular Meshwork - metabolism</topic><topic>Trabecular Meshwork - pathology</topic><topic>Traditional Chinese medicine</topic><topic>Transforming growth factor-b1</topic><topic>Transforming growth factors</topic><topic>Vascularization</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Na</creatorcontrib><creatorcontrib>Zhang, Zhang</creatorcontrib><creatorcontrib>Chen, Pei</creatorcontrib><creatorcontrib>Zhong, Yimin</creatorcontrib><creatorcontrib>Cai, Xiaoxiao</creatorcontrib><creatorcontrib>Hu, Huan</creatorcontrib><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Li, Kaijing</creatorcontrib><creatorcontrib>Ge, Jian</creatorcontrib><creatorcontrib>Yu, Keming</creatorcontrib><creatorcontrib>Liu, Xing</creatorcontrib><creatorcontrib>Zhuang, Jing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Na</au><au>Zhang, Zhang</au><au>Chen, Pei</au><au>Zhong, Yimin</au><au>Cai, Xiaoxiao</au><au>Hu, Huan</au><au>Yang, Ying</au><au>Zhang, Jing</au><au>Li, Kaijing</au><au>Ge, Jian</au><au>Yu, Keming</au><au>Liu, Xing</au><au>Zhuang, Jing</au><au>Yuan, Fan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-14</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0133055</spage><epage>e0133055</epage><pages>e0133055-e0133055</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells.
CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2.
Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26275042</pmid><doi>10.1371/journal.pone.0133055</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-08, Vol.10 (8), p.e0133055-e0133055 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2043684133 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Accumulation Adolescent Adult Apoptosis Blotting, Western Bone morphogenetic proteins Cancer Cell Cycle - drug effects Cell migration Cell Movement - drug effects Cell Survival - drug effects Cells, Cultured Chemokine CXCL12 - genetics Chemokine CXCL12 - metabolism Chemokines CXCR4 protein Cytokines Degeneration Dexamethasone Drugs, Chinese Herbal - chemistry Extracellular matrix Female Glaucoma Glioma cells Gliomas Glucocorticoids Herbal medicine Humans Hypertension Immunohistochemistry Laboratories Male Medicine Middle Aged Morphology Neovascularization Ophthalmology Patients Pharmacology Physiological aspects Polymerase chain reaction Prognosis Pulmonary fibrosis Pyrazines - chemistry Pyrazines - pharmacology Real-Time Polymerase Chain Reaction Receptors, CXCR4 - genetics Receptors, CXCR4 - metabolism SDF-1 protein Surgery Trabecular Meshwork - drug effects Trabecular Meshwork - metabolism Trabecular Meshwork - pathology Traditional Chinese medicine Transforming growth factor-b1 Transforming growth factors Vascularization Young Adult |
| title | Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis |
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