OBJECTIVE: To compare the mRNA level of cell proliferation-related genes Twist1, SIRT1, FGF2 and TGF-β3 in placenta mesenchymal stem cells (PA-MSCs), umbilical cord mensenchymals (UC-MSCs) and dental pulp mesenchymal stem cells (DP-MSCs). METHODS: The morphology of various passages of PA-MSCs, UC-MSCs and DP-MSCs were observed by microscopy. Proliferation and promoting ability of the three cell lines were detected with the MTT method. Real-time PCR (RT-PCR) was used to determine the mRNA levels of Twist1, SIRT1, FGF2, TGF-β3. RESULTS: The morphology of UC-MSCs and DP-MSCs was different from that of PA-MSCs. Proliferation ability and promoting ability of the PA-MSCs was superior to that of UC-MSCs and DP-MSCs. In PA-MSCs, expression level of Twist1 and TGF-β3 was the highest and FGF2 was the lowest. SIRT1 was highly expressed in UC-MSCs. With the cell subcultured, different expression levels of Twist1, SIRT1, FGF2, TGF-β3 was observed in PA-MSCs, UC-MSCs and DP-MSCs. CONCLUSION Up-regulated expression of the Twist1, SIRT1 and TGF-β3 genes can promote proliferation of PA-MSCs, UC-MSCs and DP-MSCs, whilst TGF-β3 may inhibit these. The regulatory effect of Twist1, SIRT1, FGF2 and TGF-β3 genes on PA-MSCs, UC-MSCs and DP-MSCs are different.
Cell Differentiation ; Cell Proliferation/genetics* ; Cells, Cultured ; Dental Pulp/cytology* ; Female ; Fibroblast Growth Factor 2/genetics* ; Humans ; Mesenchymal Stem Cells/cytology* ; Nuclear Proteins/genetics* ; Placenta/cytology* ; Pregnancy ; Sirtuin 1/genetics* ; Transforming Growth Factor beta3/genetics* ; Twist-Related Protein 1/genetics* ; Umbilical Cord/cytology*

BACKGROUND: Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated. MATERIALS AND METHODS: In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF-β induced differentiation. Activation of the TGF-β pathway and the ability of TGF-β to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis. RESULTS AND CONCLUSIONS: In this report, we show that three isoforms of TGF-β have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF-β superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF-β induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.
Activins ; Animals ; Blotting, Western ; Cell Death ; Luciferases ; Mice ; Microscopy ; Phosphorylation ; Placenta ; Protein Isoforms ; Response Elements ; Signal Transduction ; Stem Cells ; Transcriptional Activation ; Transforming Growth Factor beta ; Trophoblasts

BACKGROUND: Rosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice. METHODS: Sixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta (250 microg) was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA) for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test. RESULTS: On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-beta1 expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA. CONCLUSIONS: Rose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.
Animals ; Enzyme-Linked Immunosorbent Assay ; Epidermal Growth Factor ; Medicine, Traditional ; Mice* ; Photography ; Placenta* ; Rosa ; Transforming Growth Factor beta1 ; Vascular Endothelial Growth Factor A ; Wound Healing* ; Wounds and Injuries*

OBJECTIVETo explore the correlation between methylation of insulin-like growth factor 1 (IGF-1) gene promoter and its placenta-specific expression and fetal macrosoma.

METHODSOne hundred twenty nine healthy pregnant women were recruited between April 2011 and March 2012. Baseline data were collected with self-report questionnaires. Real-time quantitative PCR was used to determine the expression of IGF-1 mRNA in the placenta. Methylation level of the IGF 1 gene was determined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

RESULTSThe expression of IGF-1 in placenta and its methylation level showed no significant difference between macrosomic fetuses and controls. No linear correlation was found between IGF-1 mRNA expression and methylation level of IGF-1 promoter (r=0.128, P=0.295). IGF-1 promoter region in placenta showed a hypomethylation status. However, a positive correlation was found between IGF-1 expression and birth weight below 4260 g (r=0.264, P=0.022). The expression of IGF-1 mRNA was significantly higher in those with a birth weight below 4260 g, which suggested that placental IGF-1 expression may contribute to increased birth weight. In regard to fetal overgrowth, however, there seemed to be a negative correlation in which placental IGF-1 expression was downregulated to limit fetal overgrowth.

CONCLUSIONNo linear correlation was found between placental IGF-1 expression and methylation level of IGF-1 promoter with a hypomethylation status. The contribution of placental IGF-1 expression to birth weight is bidirectional. Increased expression seems to promote fetal growth, while decreased expressions may curb overgrowth, therefore control fetal growth in a relatively normal range.

Birth Weight ; DNA Methylation ; Female ; Fetal Macrosomia ; genetics ; Humans ; Infant, Newborn ; Insulin-Like Growth Factor I ; genetics ; Placenta ; metabolism ; Pregnancy ; Promoter Regions, Genetic ; RNA, Messenger ; analysis

OBJECTIVETo investigate the therapeutic effects of hemin, an inducer of heme oxygenase, in a rat model of gestational hypertension and explore the possible mechanism.

METHODSEighteen pregnant SD rats at day 12 of gestation were randomized equally into gestational hypertension model group, hemin treatment group, and normal pregnancy (control) group. In the former two groups, the rats were subjected to daily nitro-L-arginine methyl ester (L-NAME, 80 mg/kg) gavage since gestational day 14 for 7 consecutive days to induce gestational hypertension; saline was administered in the same manner in the control rats. The rats in hemin group received daily intraperitoneal injection of hemin (30 mg/kg) starting from gestational day 16. HO activity and carboxyhemoglobin (COHb) level in rat placental tissue were detected with spectrophotometric method, and soluble vascular endothelial growth factor receptor-1 (sFlt-1) and vascular endothelial growth factor (VEGF) level in the placental tissue homogenate supernatant were detected using ELSIA.

RESULTSAt gestational day 20, the blood pressure and 24-h urinary protein were significantly higher in the model group than in the other two groups (P<0.05), and were higher in hemin group than in the control group (P<0.05); HO activity and COHb content in the placenta tissue were the lowest in the model group (P<0.05), and was lower in hemin group than in the control group (P<0.05). The level of sFlt-1 was significantly higher and VEGF level significantly lower in the model group than in the other two groups (P<0.05); sFlt-1 level remained higher and VEGF lower in hemin group than in the control group (P<0.05).

CONCLUSIONHemin can reduce blood pressure and urinary protein in rats with gestational hypertension possibly by up-regulating HO activity, enhancing carbon monoxide production, reducing sFlt-1 and increasing VEGF in the placental tissue.

Animals ; Blood Pressure ; Carbon Monoxide ; metabolism ; Disease Models, Animal ; Female ; Heme Oxygenase (Decyclizing) ; Hemin ; pharmacology ; Hypertension, Pregnancy-Induced ; drug therapy ; Placenta ; drug effects ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

OBJECTIVE: To examine the circulating levels of miR-214 in acute myocardial infarction (AMI) patients and to explore the relationship between the circulating levels of miR-214 and the degree of coronary lesion. METHODS: A total of 45 patients with AMI (AMI group) were enrolled from Xiangya Hospital of Central South University between September, 2011 and January, 2012. Twenty healthy volunteers served as a normal control group (n=20). According to the coronary artery lesion area, AMI group was also divided into a single-branch group, a double-branch group and a triple-branch group (n=20, 13, 12 respectively). Circulating levels of miR-214 and plasma levels of placental growth factor (PLGF) were measured by real time-PCR assay and enzyme-linked immunosorbent assay respectively on the day when the patients admitted to the hospital. The plasma levels of miR-214 and PLGF were compared among the various branch groups. The correlation between miR-214 and PLGF was analyzed in AMI subgroups. RESULTS: The miR-214 levels in the AMI subgroups were lower than that in the control group. The more decrease in miR-214 level, the larger size of coronary lesion. There was significant difference in the different groups (all P<0.05). Compared with the control group, the levels of plasma PLGF were significantly higher in the AMI subgroups. The more increase in PLGF level, the larger size of coronary lesion. There was significant difference in the different groups (all P<0.05). The plasma levels of miR- 214 were negatively correlated with that of PLGF in the AMI group (r=-0.588, P<0.01). CONCLUSION The circulating level of miR-214 was significantly decreased in the AMI group, which might be correlated with the extent of the coronary lesion. Circulating miR-214 may be a promising biomarker for the diagnosis and prognosis of severe AMI.
Biomarkers ; blood ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Humans ; MicroRNAs ; blood ; Myocardial Infarction ; pathology ; Placenta Growth Factor ; Pregnancy Proteins ; blood ; Prognosis

OBJECTIVETo investigate the effect of placental growth factor (PlGF) on revascularization after acute myocardial infarction.

METHODSMyocardial infarction model was established by ligation of left anterior descending coronary artery in Wistar rats. Thirty AMI rats were divided into 3 groups with 10 in each group: PlGF, mouse VEGFR-1/Flt-1 antibody, or saline (control group) was injected in the infarcted border zone for each group, respectively. Two weeks later the hemodynamics parameters were measured with a left ventricular needle catheter and a biological signal analysis system; left ventricular remodeling was observed by HE staining; angiogenesis was examined by immunohistochemistry and cardiomyocyte apoptosis rate was detected by TUNEL.

RESULTSThe stroke volume, systolic pressure and left ventricular developed pressure in PlGF group were all higher than those in control group (112±7 vs 65.63±8.50 μl, P<0.01; 131.61±9.26 vs 94.84±8.53 mm Hg, P<0.01 and 175.85±11.36 vs 105.50±15.83 mm Hg, P<0.01; respectively). PlGF animals had less ventricular dilation (left ventricular diameter 8.20±0.14 vs 9.25±0.32 mm, P<0.01) and increased left ventricular wall thickness (1.81±0.10 vs 1.35±0.10 mm, P<0.01) compared to controls. The geometry parameter of anti-VEGFR1 and control animals was almost the same. PlGF animals had increased angiogenesis compared to controls (29.44±5.75 vs 15.88±2.42 endothelial cells/high-powered field, P<0.01); the alpha smooth muscle actin (α-SMA) showed that PlGF animal had a higher density of artery than others (25.14±1.83 vs 19.70±2.52 arteries/mm(2), P<0.01), and the density of artery in anti-VEFGR1 group was less than the controls. The apoptosis rate of cardiomyocytes in PlGF animals was significantly lower than that in controls (9.51%±2.75% vs 37.81%±8.74%, P<0.01).

CONCLUSIONRegional delivery of PlGF following acute myocardial infarction can improve cardiac function and left ventricular remodeling, enhance angiogenesis and reduce cardiomyocyte apoptosis rate. PlGF may be a potential agent in adjuvant therapy for acute myocardial infarction.

Animals ; Apoptosis ; drug effects ; Disease Models, Animal ; Male ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Myocardium ; pathology ; Neovascularization, Physiologic ; drug effects ; Placenta Growth Factor ; Pregnancy Proteins ; therapeutic use ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

Placenta is an important organ to maintain fetal growth, metabolism, maternal and fetal physiologic balance. Angiogenesis is a critical factor in placental development involved in fetal blood circulation and vascular changes in the endometrium and placenta. Angiogenesis is closely related to angiogenesis factors such as vascular endothelial growth factor and placenta growth factor. Fetal growth restriction threats the fetal health in gestation and also increases the long-term likeliness of several diseases. In this review, the authors summarize the findings in current studies of the relationship between angiogenesis factors and fetal growth restriction.
Angiogenesis Inducing Agents ; metabolism ; Endometrium ; blood supply ; Female ; Fetal Development ; Fetal Growth Retardation ; Humans ; Neovascularization, Physiologic ; Placenta ; blood supply ; Placenta Growth Factor ; Pregnancy ; Pregnancy Proteins ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.
Acceleration ; Animals ; Biopsy ; Collagen ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors ; Humans ; Immunohistochemistry ; Inflammation ; Mice* ; Placenta* ; Skin ; Wound Healing* ; Wounds and Injuries

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.
Acceleration ; Animals ; Biopsy ; Collagen ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors ; Humans ; Immunohistochemistry ; Inflammation ; Mice* ; Placenta* ; Skin ; Wound Healing* ; Wounds and Injuries