Abstract:
:The present study aimed to assess the effects of therapy with adiponectin (APN) gene-modified adipose-derived stem cells (ADSCs) on pulmonary arterial hypertension (PAH) in rats and the underlying cellular and molecular mechanisms. ADSCs were successfully isolated from the rats and characterized. ADSCs were effectively infected with the green fluorescent protein (GFP)-empty (ADSCs-V) or the APN-GFP (ADSCs-APN) lentivirus and the APN expression was evaluated by ELISA. Sprague-Dawley rats were administered monocrotaline (MCT) to develop PAH. The rats were treated with MCT, ADSCs, ADSCs-V and ADSCs-APN. Then ADSCs-APN in the lung were investigated by confocal laser scanning microscopy and western blot analysis. Engrafted ADSCs in the lung were located around the vessels. Mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RVHI) in the ADSCs-APN-treated mice were significantly decreased as compared with the ADSCs and ADSCs-V treatments. Pulmonary vascular remodeling was assessed. Right ventricular (RV) function was evaluated by echocardiography. We found that pulmonary vascular remodeling and the parameters of RV function were extensively improved after ADSCs-APN treatment when compared with ADSCs and ADSCs-V treatment. Pulmonary artery smooth muscle cells (PASMCs) were isolated from the PAH rats. The antiproliferative effect of APN on PASMCs was assayed by Cell Counting Kit-8. The influence of APN and specific inhibitors on the levels of bone morphogenetic protein (BMP), adenosine monophosphate activated protein kinase (AMPK), and small mothers against decapentaplegia (Smad) pathways was detected by western blot analysis. We found that APN suppressed the proliferation of PASMCs isolated from the PAH rats by regulating the AMPK/BMP/Smad pathway. This effect was weakened by addition of the AMPK inhibitor (compound C) and BMP2 inhibitor (noggin). Therefore, combination treatment with ADSCs and APN effectively attenuated PAH in rats by inhibiting PASMC proliferation and regulating the AMPK/BMP/Smad pathway.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Luo L,Zheng W,Lian G,Chen H,Li L,Xu C,Xie Ldoi
10.3892/ijmm.2017.3226subject
Has Abstractpub_date
2018-01-01 00:00:00pages
51-60issue
1eissn
1107-3756issn
1791-244Xjournal_volume
41pub_type
杂志文章abstract::Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key element in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Moreover, it is a negative regulator of autophagy and acts as a central regulator in cell growth. For the treatment of cancer, mTOR is a nove...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1282
更新日期:2013-04-01 00:00:00
abstract::Arachidin-1 [trans-4-(3-methyl-1-butenyl)-3,5,3',4'-tetrahydroxystilbene] is a polyphenol produced by peanut kernels during germination. The aim of the present study was to investigate the mechanism underlying the anti-inflammatory effect of arachidin-1 in endothelial cells (ECs). The results of cell adhesion and west...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3238
更新日期:2018-01-01 00:00:00
abstract::p57 (Kip2) belongs to the Cip/Kip family and is one of the universal negative regulators of the cell cycle. In this study, we investigated the p57 expression of various types of thyroid neoplasm. p57 overexpression was observed in only 4.2% of normal thyroid tissues. In follicular adenoma and minimally invasive follic...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) occurs in patients with components of metabolic syndrome such as type 2 diabetes mellitus (T2DM). At present, the central pathophysiological problem in patients afflicted with NAFLD is insulin resistance. In this study, we aimed to determine the effects of a dipeptidyl peptida...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.2899
更新日期:2017-04-01 00:00:00
abstract::Endogenous molecules released by dying cells [i.e., damage-associated molecular patterns (DAMPs)] after trauma and severe blood loss can activate pattern recognition receptors, leading to a cascade of inflammatory responses and organ injury. Mitochondrial transcription factor A (TFAM) is a transcription factor for mit...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2012.959
更新日期:2012-07-01 00:00:00
abstract::Fruits, vegetables, spices and a variety of teas are suggested for the prevention of many diseases. They encompass active, non-nutritional ingredients called nutraceuticals which are defined as food products that provide health benefits. Many nutraceuticals have been tested to identify inhibitors of plasminogen activa...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.615
更新日期:2011-04-01 00:00:00
abstract::Metformin, a widely prescribed antidiabetic drug, has previously been shown to lower the risk of certain types of cancer, including that of breast cancer, and to improve prognosis. Its anticancer effects, which are mediated by the activation of AMP-activated protein kinase (AMPK), have become notable. The Sonic hedgeh...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2217
更新日期:2015-07-01 00:00:00
abstract::Following the publication of the above paper, the authors noted that the first author affiliation was presented incorrectly. Essentially, 'School of Medicine' had been omitted from the address. Therefore, the author and affiliation details for this paper should have been presented as follows (the changes are highlight...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,已发布勘误
doi:10.3892/ijmm.2019.4422
更新日期:2020-02-01 00:00:00
abstract::The family of chromosomal high mobility group I/Y consists of proteins involved in gene regulation and chromatin organization. A common feature of these proteins is the presence of multiple copies of DNA binding domains (DBD), the so-called AT-hooks. Bi- or tridendate interaction of two or three DBDs with appropriatel...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.6.4.409
更新日期:2000-10-01 00:00:00
abstract::The miR-200 family was recently identified as a suppressor of epithelial-mesenchymal transition (EMT). The loss or gain of miR-200 family members is associated with cancer invasion. The epidermal growth factor receptor (EGFR) is overexpressed in the majority of anaplastic thyroid cancers (ATCs). The activation of EGFR...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2012.1059
更新日期:2012-10-01 00:00:00
abstract::Heparanase is an enzyme that degrades extracellular glycoprotein to release heparan sulfate molecules. CD44 variant exon 3 (CD44v3), a receptor for heparan sulfate, generates intracellular signals for cell migration. Production of CD44v3 and expression of heparanase were detected by immunohistochemistry and in situ hy...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::The purpose of this study is to extract common features of an environmental hormone-oriented neoplasia by comparatively investigating the epidemiological characteristics of testicular cancer in Denmark with those of other cancers, of which the age-adjusted incidence rates (AAIRs) underwent remarkable increase or decre...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2.6.705
更新日期:1998-12-01 00:00:00
abstract::Substantial evidence has indicated that osteoblastic differentiation may be regulated by mechanical loads or bone morphogenetic protein-2 (BMP-2). BMP-2-induced in vivo osteogenesis can be significantly enhanced in the presence of mechanical stimuli, revealing the therapeutic potential of the combined application of B...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2354
更新日期:2015-11-01 00:00:00
abstract::Estrogen receptors (ER) are present in various reproductive tissues as well as in other tissues not considered classical targets for estrogen. A variety of alternatively spliced ER variants which co-exist with the wild-type receptor has also been described in many tissues. We analyzed the presence of both wild-type an...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.5.3.223
更新日期:2000-03-01 00:00:00
abstract::We analyzed a series of ovarian carcinomas from patients treated with cisplatin-based chemotherapy for loss of heterozygosity (LOH) to determine the relationship between microsatellite alteration and prognosis. Patients with tumors that had lost alleles at loci 3p14-21, 12qter, or 17p13.3 showed significantly reduced ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulator...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.2018.3689
更新日期:2018-08-01 00:00:00
abstract::Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the effects of mycelium extracts of P. linteus (MEPL) on the growth of human neu...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2004-08-01 00:00:00
abstract::Atrial natriuretic peptide (ANP) is a regulatory hormone widely expressed, along with its receptors, in organs and body tissues. ANP is well known to inhibit aldosterone secretion from mammalian adrenals, but its effect on glucocorticoid-hormone production is controversial. In vivo experiments showed that prolonged AN...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-04-01 00:00:00
abstract::The advanced glycation end‑product (AGE)‑receptor for AGE (RAGE) axis induces transforming growth factor‑β (TGF‑β) expression, cell hypertrophy and increases extracellular matrices that are indicated in the pathogenesis of diabetic nephropathy (DN). RAGE binds to numerous ligands besides AGE, including S100B. In the p...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2024
更新日期:2015-02-01 00:00:00
abstract::Exposure of the skin to ultraviolet (UV) radiation causes extracellular matrix (ECM) collapse in the dermis, owing to an increase in matrix metalloproteinase (MMP) production in both the epidermis and dermis, and a decrease in type I collagen expression in the dermis. Recently, black rice (Oryza sativa L.) was reporte...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3508
更新日期:2018-05-01 00:00:00
abstract::The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) plays a crucial role in the initiation of atherosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important molecules involved in the adhesion of monocytes to HUVECs. Previous studies...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2579
更新日期:2016-06-01 00:00:00
abstract::Cancer development is associated with the high mobility group box protein 1 (HMGB1), which modulates the transcriptional activity in the nucleus, but it is also present in the cytoplasm and outside the cell in certain conditions. As the progression of lung cancer is supported by mitogenic stimuli of stromal fibroblast...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2007-08-01 00:00:00
abstract::The elevation of natural killer cell activity (NKCA) by laughter was not confirmed due to incomplete methodology of previous studies although positive emotion is believed to be favorable for health. To verify NKCA elevation by laughter in a crossover design, we measured NKCA before and after watching films, presenting...
journal_title:International journal of molecular medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.3892/ijmm.8.6.645
更新日期:2001-12-01 00:00:00
abstract::Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP a...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3028
更新日期:2017-08-01 00:00:00
abstract::Previously, a specific angiogenesis inhibitor, angiostatin, discovered in urine and serum of tumor-bearing mice, was reported to potently block tumor growth and metastasis in animal models. Detection of angiostatin and its precursor proteins in urine from cancer patients has not been reported. Now, we report the devel...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.5.5.547
更新日期:2000-05-01 00:00:00
abstract::p107 protein, a member of the retinoblastoma family protein, suppresses growth promotion in cancer cells. We have already reported evidence that calpain, a calcium dependent protease is involved in the cleavage of p107 protein. We show here that p107 protein can also be a substrate for ubiquitination. A negative growt...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.4.5.487
更新日期:1999-11-01 00:00:00
abstract::Congenital heart disease (CHD), the most prevalent birth defect in humans worldwide, is still a leading non‑infectious cause of infant morbidity and mortality. Increasing evidence demonstrates that genetic risk factors play a key role in the pathogenesis of CHD, and more than 50 genes have been linked to various types...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2077
更新日期:2015-04-01 00:00:00
abstract::Angiogenesis is regulated by various factors. In particular, VEGF and basic FGF are of much importance. We found that 8-(3-oxo-4,5,6-trihydroxy-3h-xanthen-9-yl)-1-naphthoic acid inhibited the binding of VEGF to KDR/Flk-1 (VEGF receptor-2) or Flt-1 (VEGF receptor-1) and that it inhibited the MAPK phosphorylation in HUV...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2.2.211
更新日期:1998-08-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was used in which 3T3-L...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2085
更新日期:2015-04-01 00:00:00
abstract::The existence of at least two distinct alpha 1,2fucosyltransferases has been postulated for many years, and recently confirmed in humans with the cloning of the human and rabbit secretor type alpha 1,2fucosyltransferase. We now describe the cloning and analysis of PFUT2, the pig secretor type alpha 1,2fucosyltransfera...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.3.2.199
更新日期:1999-02-01 00:00:00