Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway

Zhang, Xiaoping; Mao, Haian; Chen, Jin‐Yuan; Wen, Sheng-Jun; Li, Dan; Ye, Meng; Lv, Zhongwei

doi:10.1016/j.bbrc.2012.12.157

Cited by 55 publications

(37 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a specific miRNA identified in human umbilical vein endothelial cells (HUVECs), miR-221 participates in the regulation of angiogenesis [53]. Previous findings demonstrate that miR-221 inhibits the proliferation of endothelial progenitor cells (EPC) via interactions with the MEK/ERK pathway, thereby indicating a potential role of miR-221 for maintaining the integrity of the endothelium [54]. Interestingly, treatment with atorvastatin increased EPC numbers and decreased miR-221/222 levels in patients with CHD [55].…”

Section: Discussionmentioning

confidence: 99%

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China

Jia

Chen

Ding

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD. Subject and method: 932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2^-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores. Result: The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p = <0.001), miR-155 (OR, 1.520; 95 % CI, 1.132-2.042, p = 0.005), and miR-130a (OR, 1.943; 95% CI, 1.410-2.678, p = <0.001) were potential risk factors for CHD. Moreover, miR-130a (OR, 2.405; 95 % CI, 1.691-3.421, p = <0.001) remained independently associated with the risk of CHD after adjusting for potential confounding factors. The analysis of the possible positive/negative associations between miR-221, miR-155 and miR-130awere conducted. A positive association between miR-130a and miR-155 was found (SI = 1.60, SIM = 1.21 and AP = 0.22), and in these groups, the proportion of CHD attributable to the interaction between miR-130a and miR-155 was as high as 22 %. A negative interaction was found between miR-221 and miR-130a (SI = 0.68, SIM = 0.60 and AP = 0.27). Conclusion: Plasma levels of miR-221, miR-130a and miR-155 decreased in patients with CHD, and miR-130a may be an independent predictor for CHD.

show abstract

Section: Discussionmentioning

confidence: 99%

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China

Jia

Chen

Ding

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Several studies including our own link PAK1 to ERK1/2 [5], [44], [50]. Loss of PAK1 results in downregulation of ERK activity with negative effects on cell motility/migration [29], [78], and proliferation [79]. Furthermore, PAK1 activation induced by adhesion to matrix proteins activates the MAPK signaling cascade and is thought to be a convergence site between integrins and growth factor signaling [80], [81].…”

Section: Discussionmentioning

confidence: 89%

Potential Compensation among Group I PAK Members in Hindlimb Ischemia and Wound Healing

et al. 2014

View full text Add to dashboard Cite

PAKs are serine/threonine kinases that regulate cytoskeletal dynamics and cell migration. PAK1 is activated by binding to the small EF hand protein, CIB1, or to the Rho GTPases Rac1 or Cdc42. The role of PAK1 in angiogenesis was established based only on in vitro studies and its role in angiogenesis in vivo has never been examined. Here we tested the hypothesis that PAK1 is an essential regulator of ischemic neovascularization (arteriogenesis and angiogenesis) and wound healing using a global PAK1 knockout mouse. Neovascularization was assessed using unilateral hindlimb ischemia. We found that plantar perfusion, limb use and appearance were not significantly different between 6–8 week old PAK1−/− and PAK1+/+ mice throughout the 21-day period following hindlimb ischemia; however a slightly delayed healing was observed in 16 week old PAK1−/− mice. In addition, the wound healing rate, as assessed with an ear punch assay, was unchanged in PAK1−/− mice. Surprisingly, however, we observed a notable increase in PAK2 expression and phosphorylation in ischemic gastrocnemius tissue from PAK1−/− but not PAK1+/+ mice. Furthermore, we observed higher levels of activated ERK2, but not AKT, in ischemic and non-ischemic muscle of PAK1−/− mice upon hindlimb ischemic injury. A group I PAK inhibitor, IPA3, significantly inhibited endothelial cell sprouting from aortic rings in both PAK1−/− and PAK1+/+ mice, implying that PAK2 is a potential contributor to this process. Taken together, our data indicate that while PAK1 has the potential to contribute to neovascularization and wound healing, PAK2 may functionally compensate when PAK1 is deficient.

show abstract

“…A previous investigation showed that the level of miR-221 in EPCs was higher in patients with coronary artery disease and the miR-221 expression inversely correlated with the number of EPCs [30]. Zhang X et al further demonstrated that miR-221 overexpression inhibited the proliferation of endothelial progenitor cells by directly targeting PAK1 and affecting the c-Raf/MEK/ERK pathway [31]. An in vivo study in rats also indicated that the downregulation of miR-221 and miR-222 can reduce the proliferation of VSMCs and neointimal hyperplasia, both of which play important roles in arterial restenosis after intima injury [32].…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs have a sex-specific association with metabolic syndrome

et al. 2013

View full text Add to dashboard Cite

BackgroundThe microRNAs let-7 g and miR-221 have been demonstrated to be related to the glucose metabolism. This study assessed the serum levels of these two microRNAs in subjects with and without metabolic syndrome (MetS).ResultsThe serum microRNA levels were detected in 102 subjects aged 40 to 80 years who were recruited from the general population. The status of MetS was defined by the Adult Treatment Panel III (ATP III) criteria modified for Asians. Subjects with histories of cardiovascular diseases or who were receiving treatment with hypoglycemic or lipid-lowering agents were excluded. The levels of both circulating microRNAs (let-7 g and miR-221) were higher in subjects with MetS (p = 0.004 and p = 0.01, respectively). The sex-specific analysis showed that the difference was more prominent in women (for both miRNAs, p < 0.05 in women and p > 0.1 in men). In the female subjects, increased expression of both microRNAs was associated with an increased number of MetS risk components (p = 0.002 for let-7 g and p = 0.022 for miR-221). Moreover, the elevation of serum let-7 g was significantly associated with a low level of high-density lipoprotein cholesterol (p = 0.022) and high blood pressure (p = 0.023). In contrast, the miR-221 level was not associated with any individual MetS risk component.ConclusionsThe circulating levels of let-7 g and miR-221 displayed a female-specific elevation in individuals with metabolic syndrome.

show abstract

Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway

Cited by 55 publications

References 22 publications

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China

Potential Compensation among Group I PAK Members in Hindlimb Ischemia and Wound Healing

Circulating microRNAs have a sex-specific association with metabolic syndrome

Contact Info

Product

Resources

About