CTRP6 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration.

Vascular smooth muscle cell (VSMC) proliferation and migration play critical roles in the development and progression of atherosclerosis. C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs family, was involved in cardiovascular diseases, inflammatory reaction and adipogenesis. However, the role of CTRP6 in VSMCs remains largely unknown. The purpose of this study is to investigate the effects of CTRP6 on VSMC proliferation and migration and explore the possible mechanism. Our results indicated that CTRP6 expression was dramatically down-regulated in human atherosclerotic tissues and in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB). In addition, CTRP6 overexpression significantly inhibited the proliferation and migration of VSMCs exposed to PDGF-BB, as well as increased expression of α-SMA and SM22α in PDGF-BB-stimulated VSMCs. Furthermore, CTRP6 overexpression efficiently prevented the activation of PI3K/Akt/mTOR in VSMCs in response to PDGF-BB. In conclusion, these findings showed that CTRP6 inhibits PDGF-BB-induced VSMC proliferation and migration, at least in part, through suppressing the PI3K/Akt/mTOR signaling pathway. Therefore, CTRP6 may be a potential target for the treatment of atherosclerosis.

Aberrant estrogen receptor alpha expression correlates with hepatocellular carcinoma metastasis and its mechanisms.

BACKGROUND/AIMS: Metastasis one of the obstacles before poor prognosis of hepatocellular carcinoma (HCC) is improved. Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of HCC. However, the molecular mechanism of ERalpha in mediating HCC metastasis is still unclear. The aim of the present study was to detect aberrant ERalpha expression in HCC and elucidate its possible mechanisms in HCC metastasis. METHODOLOGY: We detected expression of ERalpha, phospho-estrogen receptor alpha (p-ERalpha), nuclear factor kappa B (NF-kappaB) p65 and Matrix metalloproteinase-9 (MMP-9) between HCC tissues with portal vein tumor thrombus (PVTT) and those without PVTT by immunohistochemical method. Moreover, the expression of above parameters was also determined in HCC cells of different metastatic potential by using immunocytochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. RESULTS: The expression of ERalpha and p-ERalpha was lower in HCC with PVTT than those without PVTT. Meanwhile, the expression pattern of above parameters was also similar in HCC cells of different metastatic potential, whereas, the expression of NF-kappaB p65 and MMP-9 was higher in HCC with PVTT than those without PVTT. The expression of NF-kappaB p65 and MMP-9 in HCC cells was also analogous to the tissues. CONCLUSIONS: These results demonstrated that expression of ERalpha, p-ERalpha, NF-kappaB p65 and MMP-9 correlated with invasion and metastasis in HCC. The mechanism of HCC metastasis may mediate through cross-talk between the NF-KB and ER signaling pathways. Meanwhile, ERa regulated MMP-9 through NF-kappaB indirectly.