Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ.
Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ.
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University , Changchun 130041, China.
Duo
D
Zhao
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University , Changchun 130041, China.
Zhicheng
Z
Zhu
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University , Changchun 130041, China.
Dan
D
Li
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University , Changchun 130041, China.
Rihao
R
Xu
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University , Changchun 130041, China.
Tiance
T
Wang
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University , Changchun 130041, China.
Kexiang
K
Liu
D001549:Benzamides / Q000494:pharmacology; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003131:Combined Modality Therapy; D003864:Depression, Chemical; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D015536:Down-Regulation; D016894:Endarterectomy, Carotid; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D047493:PPAR alpha / Q000187:drug effects / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D000077205:Pioglitazone; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
C501896:ACKR3 protein, human; D001549:Benzamides; D047493:PPAR alpha; D047495:PPAR gamma; D011725:Pyridines; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; C458508:T 0070907; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone