Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

Zhou, Sijing; Li, Min; Zeng, Daxiong; Zhu, Zhongming; Hu, Xueyang; Yong-huai, LI; Wang, Ran; Sun, Guibo

doi:10.1038/srep08564

Cited by 18 publications

(19 citation statements)

References 41 publications

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“…This result suggests that smoking is associated with increased plasma CTGF levels in type 1 diabetic patients. This lends support to previous findings that CTGF expression levels in pulmonary vessels isolated from smokers was higher than those from nonsmokers [ 26 ].…”

Section: Resultssupporting

confidence: 91%

Analysis of longitudinal semicontinuous data using marginalized two-part model

et al. 2018

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BackgroundConnective tissue growth factor (CTGF), is a secreted matricellular factor that has been linked to increased risk of cardiovascular disease in diabetic subjects. Despite the biological role of CTGF in diabetes, it still remains unclear how CTGF expression is regulated. In this study, we aim to identify the clinical parameters that modulate plasma CTGF levels measured longitudinally in type 1 diabetic patients over a period of 10 years. A number of patients had negligible measured values of plasma CTGF that formed a point mass at zero, whereas others had high positive values of CTGF that were measured on a continuous scale. The observed combination of excessive zero and continuous positively distributed non-zero values in the CTGF outcome is referred to as semicontinuous data.MethodsWe propose a novel application of a marginalized two-part model (mTP) extended to accommodate longitudinal semicontinuous data in which the marginal mean is expressed in terms of the covariates and estimates of their effect on the mean responses are generated. The continuous component is assumed to follow distributions that stem from the generalized gamma family whereas the binary measure is analyzed using logistic model and both have correlated random effects. Other approaches including the one- and two-part with uncorrelated and correlated random effects models were also applied and their estimates were all compared.ResultsOur results using the mTP model identified intensive glucose control treatment and smoking as clinical factors that were associated with decreased and increased odds of observing non-zero CTGF values respectively. In addition, hemoglobin A1c, systolic blood pressure, and high density lipoprotein were all shown to be significant risk factors that contribute to increasing CTGF levels. These findings were consistently observed under the mTP model but varied with the distributions for the other models. Accuracy and precision of the mTP model was further validated using simulation studies.ConclusionThe mTP model identified new clinical determinants that modulate the levels of CTGF in diabetic subjects. Applicability of this approach can be extended to other biomarkers measured in patient populations that display a combination of negligible zero and non-zero values.

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Section: Resultssupporting

confidence: 91%

Analysis of longitudinal semicontinuous data using marginalized two-part model

et al. 2018

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“…The experiments were performed as previously described. 60 , 61 Briefly, PASMCs were seeded into 24-well plates and treated accordingly before an MTT cell proliferation assay kit (Sigma-Aldrich, St. Louis, MO, USA) was used to assay cell viability. Each experiment was performed in triplicates.…”

Section: Methodsmentioning

confidence: 99%

Identifying Involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in Treating Pulmonary Hypertension with Melatonin

Wang

Zhou

et al. 2018

Molecular Therapy - Nucleic Acids

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Non-coding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). The aim of this study was to characterize the therapeutic role of melatonin as well as the underlying molecular mechanism (its effects on the expression of H19 and its downstream signaling pathways) in the treatment of PAH. Real-time PCR and western blot analysis were performed to evaluate the expression of H19, miR-200a, miR-675, insulin-like growth factor-1 receptor (IGF1R), and programmed cell death 4 (PDCD4). The value of systolic pulmonary artery pressure (SPAP) and the ratio of medial thickening in the monocrotaline (MCT) group were increased, whereas the melatonin treatment could decrease these values to some extent. The weights of RV (right ventricle), LV (left ventricle) + IVS (interventricular septal), and RV/(LV + IVS) in the MCT group were much higher than those in the MCT + melatonin and control groups. In addition, the expression of H19, miR-675, IGF1R mRNA, and IGF1R protein in the MCT group was the highest, whereas their expression in the control group was the lowest. The expression of miR-200, PDCD4 mRNA, and PDCD4 protein in the MCT group was the lowest, whereas their expression in the control group was the highest. Furthermore, H19 directly suppressed the expression of miR-200a, whereas miR-675-3p and miR-200a directly inhibited the expression of IGF1R and PDCD4, respectively. Finally, melatonin treatment inhibited cell proliferation; upregulated the expression of H19, miR-675-3p, and PDCD4; and downregulated the expression of miR-200a and IGF1R. This study demonstrated the role of H19-miR-675-3p-IGF1R- and H19-miR-200a-PDCD4-signaling pathways in the melatonin treatment of PAH.

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“…The experiments were performed as previously described [Zhou et al, , c]. Dulbecco's modified Eagle medium (DMEM) (Invitrogen) supplement with 10% FBS (fetal bovine serum) (Life Technologies, Germany), streptomycin (100 mg/mL), penicillin (100 U/mL) was used to maintain the PASMCs in an atmosphere of 5% CO 2 in air at 37°C in accordance with the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of SRF Is Associated With Hypoxic Pulmonary Hypertension by Promoting Viability of Smooth Muscle Cells via Increasing Expression of Bcl-2

Ding

Zhou

et al. 2017

J. Cell. Biochem.

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The aim of study was to investigate the involvement of hypoxia-induced upregulation of serum response factor (SRF) and its downstream effector, B cell leukemia-2 (Bcl-2), in hypoxia-induced pulmonary hypertension (PH). Immunohistochemistry analysis and western blot analysis were used to detect the levels of SRF and Bcl-2 in rats exposed to hypoxia. Furthermore, the regulatory relationship between SRF and Bcl-2 was investigated in PASMCs using real-time PCR and western-blot analysis. We found that mPAP (mean pulmonary arterial pressure) and WA (the ratio of vascular wall area to external diameter) were increased after exposure to hypoxia, while LA (the ratio of vascular lumen area to total area) decreased after exposure to hypoxia. The immunohistochemistry analysis displayed a substantial increase in SRF and Bcl-2 in pulmonary arterial walls after 14 days of hypoxia. And the western blotting showed that SRF and Bcl-2 protein levels were much higher after 7 days of hypoxia and then remained at a high level. And then the levels of SRF and Bcl-2 in pulmonary artery smooth muscle cells (PASMCs) exposed to hypoxia were substantially suppressed following introduction of SRF siRNA, and the level of Bcl-2 was remarkably inhibited by Bcl-2 siRNA, while Bcl-2 siRNA had no effect on SRF level. Finally, SRF siRNA, and Bcl-2 siRNA significantly reduced viability of PASMCs exposed to hypoxia, and enhanced apoptosis of PASMCs exposed to hypoxia. These data validated that SRF responded to hypoxia, which subsequently was involved in pulmonary hypertension by abnormally promoting viability of PASMCs via modulating expression of Bcl-2. J. Cell. Biochem. 118: 2731-2738, 2017. © 2017 Wiley Periodicals, Inc.

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Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

Cited by 18 publications

References 41 publications

Analysis of longitudinal semicontinuous data using marginalized two-part model

Analysis of longitudinal semicontinuous data using marginalized two-part model

Identifying Involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in Treating Pulmonary Hypertension with Melatonin

Upregulation of SRF Is Associated With Hypoxic Pulmonary Hypertension by Promoting Viability of Smooth Muscle Cells via Increasing Expression of Bcl-2

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