title: Chinese medicine Tongxinluo increases tight junction protein levels by inducing KLF5 expression in microvascular endothelial cells.
abstract: Tongxinluo (TXL) is a compound prescription formulated according to the meridian theory of traditional Chinese medicine. It may play an important role in cardiovascular protection by improving endothelial cell function. The aim of present study was to investigate whether endothelial protection with TXL is related to its regulation of tight junction protein expression. Human cardiac microvascular endothelial cells (HCMECs) were cultured and treated with 10(-7)  mol l(-1) angiotensin II (Ang II) and the different doses of TXL; the expression of tight junction proteins occludin, claudin, VE-cadherin and beta-catenin was determined by Western blotting and real-time PCR. Gain-of-function and loss-of-function of Krüppel-like factor 5 (KLF5) were carried out in HCMEC transfected with either KLF5 adenovirus pAd-KLF5 or siRNA specific for KLF5. Angiotensinogen transgenic mice were treated with TXL by oral administration of TXL of 0.75 g kg(-1)  day(-1) , and immunohistochemical staining was performed with antioccludin, anticlaudin, anti-VE-cadherin, antibeta-catenin and anti-KLF5 antibodies. Ang II treatment significantly reduced the expression of tight junction proteins occludin, claudin, VE-cadherin and beta-catenin in cultured HCMECs. TXL pretreatment could abrogate the down-regulation of these tight junction proteins induced by Ang II. Ang II treatment also decreased KLF5 expression at the mRNA and protein levels; TXL pretreatment markedly reversed the inhibitory effect of Ang II on KLF5 expression. Gain-of-function and loss-of-function of KLF5 showed that KLF5 mediated the expression of tight junction proteins in HCMECs. TXL-enhanced expression of the tight junction proteins was mediated by KLF5. In angiotensinogen transgenic mice, TXL also increased the tight junction protein levels by inducing KLF5 expression. Chinese medicine TXL increases tight junction protein levels by inducing KLF5 expression in microvascular endothelial cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Ruo-Nan
authors.initials: RN
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Li-Shuang
authors.initials: LS
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Cui-Ying
authors.initials: CY
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Zong-Wei
authors.initials: ZW
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Jin-Kun
authors.initials: JK
authors.lastname: Wen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; C492214:KLF5 protein, human; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D062725:Tight Junction Proteins; C513941:tongxinluo; D000804:Angiotensin II
keywords: KLF5; angiotensin II; endothelial cell; tight junction protein; tongxinluo