scholarly journals Changes in Smad expression and subcellular localization in bleomycin-induced pulmonary fibrosis

2004 ◽  
Vol 287 (6) ◽  
pp. L1342-L1347 ◽  
Author(s):  
N. Venkatesan ◽  
L. Pini ◽  
M. S. Ludwig
Keyword(s):  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Nuclear Accumulation ◽  
Endogenous Inhibitor ◽  
Sprague Dawley ◽  
Experimental Animals ◽  
Molecular Defects ◽  
Sprague Dawley Rats ◽  
Smad Proteins ◽  
Intratracheal Injection

Administration of bleomycin (BM) produces inflammation and fibrosis of the lung in humans and experimental animals. The molecular defects by which BM induces these pathological effects have not been studied in detail. We studied the expression of Smad family proteins, key molecules involved in mediating transforming growth factor (TGF)-β signaling from the cell membrane to the nucleus, during the early and late phases of BM-induced fibrogenesis. Pulmonary fibrosis was induced in male Sprague-Dawley rats by a single intratracheal injection (1.5 units) of BM. Control rats received saline. Rats were killed at 3, 5, 7, 14, and 28 days after BM, cytosolic and nuclear proteins were extracted and isolated from lung tissues, and Smad proteins were probed with specific antibodies. In BM-exposed lung tissue, compared with control, Smad3 decreased persistently in the cytosol and increased transiently in the nucleus. There was a persistent increase in phosphorylation and nuclear accumulation of Smad2/3. Smad4 was increased transiently in both the cytosol and nucleus. A significant and progressive decrease in the expression of Smad7, the endogenous inhibitor of TGF-β/Smad signaling, was observed after BM instillation. Collectively, our results indicate that an imbalance between agonistic Smads2–4 and antagonistic Smad7 may result in the unchecked activation of an autocrine TGF-β loop, which contributes to the pathogenesis of BM-induced pulmonary fibrosis.

TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells

1999 ◽  
Vol 112 (24) ◽  
pp. 4557-4568 ◽  
Author(s):  
E. Piek ◽  
A. Moustakas ◽  
A. Kurisaki ◽  
C.H. Heldin ◽  
P. ten Dijke
Keyword(s):  
Transforming Growth Factor ◽  
Activin A ◽  
Nuclear Accumulation ◽  
Type I ◽  
Beta Catenin ◽  
Tgf Beta ◽  
Mesenchymal Transition ◽  
Smad Proteins ◽  
Mesenchymal Transformation ◽  
Alk 5

The capacities of different transforming growth factor-(beta) (TGF-(beta)) superfamily members to drive epithelial to mesenchymal transdifferentiation of the murine mammary epithelial cell line NMuMG were investigated. TGF-(beta)1, but not activin A or osteogenic protein-1 (OP-1)/bone morphogenetic protein-7 (BMP-7), was able to induce morphological transformation of NMuMG cells as shown by reorganisation of the actin cytoskeleton and relocalisation/downregulation of E-cadherin and (beta)-catenin, an effect that was abrogated by the more general serine/threonine kinase and protein kinase C inhibitor, staurosporine. TGF-(beta)1 bound to TGF-(beta) type I receptor (T(beta)R-I)/ALK-5 and T(beta)R-II, but not to activin type I receptor (ActR-I)/ALK-2. Activin A bound to ActR-IB/ALK-4 and ActR-II, and BMP-7 bound to ActR-I/ALK-2, BMP type I receptor (BMPR-I)/ALK-3, ActR-II and BMPR-II. TGF-(beta)1 and BMP-7 activated the Smad-binding element (SBE)(4) promoter with equal potency, whereas activin A had no effect. Transfection of constitutively active (CA)-ALK-4 activated the 3TP promoter to the same extent as TGF-(beta)1 and CA-ALK-5 indicating that activin signalling downstream of type I receptors was functional in NMuMG cells. In agreement with this, activin A induced low levels of plasminogen activator inhibitor I expression compared to the high induction by TGF-(beta)1. In contrast to activin A and BMP-7, TGF-(beta)1 strongly induced Smad2 phosphorylation. Consistent with these findings, TGF-(beta)1 induced the nuclear accumulation of Smad2 and/or Smad3. In addition, NMuMG cells transiently infected with adenoviral vectors expressing high level CA-ALK-5 exhibited full transdifferentiation. On the other hand, infections with low level CA-ALK-5, which alone did not result in transdifferentiation, together with Smad2 and Smad4, or with Smad3 and Smad4 led to transdifferentiation. In conclusion, TGF-(beta)1 signals potently and passes the activation threshold to evoke NMuMG cell transdifferentiation. The TGF-(beta) type I receptor (ALK-5) and its effector Smad proteins mediate the epithelial to mesenchymal transition. Activin A does not induce mesenchymal transformation, presumably because the number of activin receptors is limited, while BMP-7-initiated signalling cannot mediate transdifferentiation.

OESTROGEN-INDUCED PROTEIN IN RAT MAMMARY TUMOUR AND UTERUS

1977 ◽  
Vol 75 (2) ◽  
pp. 331-332 ◽  
Author(s):  
N. MAIRESSE ◽  
J. C. HEUSON ◽  
P. GALAND ◽  
G. LECLERCQ
Keyword(s):  
Interdisciplinary Research ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Nuclear Accumulation ◽  
Oestrogen Receptors ◽  
Sprague Dawley ◽  
Rat Uterus ◽  
Mammary Tumours ◽  
Sprague Dawley Rats ◽  
Female Genital

Biology Unit, Institute of Interdisciplinary Research, Free University of Brussels, 115 B Waterloo, 1000-Brussels, Belgium and *Service de Médecine et Laboratoire d'Investigation Clinique, Institut J. Bordet, 1000-Brussels, Belgium (Received 19 April 1977) We wish to report evidence for the early induction by oestradiol-17β of a protein in mammary tumours induced in Sprague–Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA). The protein appears to be analogous to the oestrogen-induced protein first discovered in the rat uterus by Notides & Gorski (1966) and widely known as 'induced protein' (IP). Induction of IP by oestradiol-17β has been demonstrated in rodents in several tissues of the female genital tract that are targets for oestrogens (Katzman, Larson & Podratz, 1971; Katzenellenbogen & Leake, 1974; Dupont-Mairesse & Galand, 1975) and correlated with the rate of nuclear accumulation of oestrogen receptors (Katzenellenbogen & Gorski, 1972; Katzenellenbogen, 1975). Therefore, the search for induction of IP in DMBA-induced mammary tumours containing oestrogen

scholarly journals Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II

2017 ◽  
Vol 18 (2) ◽  
pp. 147032031770665 ◽  
Author(s):  
Ning-Ping Wang ◽  
James Erskine ◽  
Wei-Wei Zhang ◽  
Rong-Hua Zheng ◽  
Li-Hui Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
At1 Receptor ◽  
Sprague Dawley ◽  
Monocyte Chemoattractant Protein 1 ◽  
Sprague Dawley Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.

Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen

2007 ◽  
Vol 293 (1) ◽  
pp. H590-H598 ◽  
Author(s):  
Eduard I. Dedkov ◽  
Wei Zheng ◽  
Lance P. Christensen ◽  
Robert M. Weiss ◽  
Florence Mahlberg-Gaudin ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Perfusion ◽  
Transforming Growth Factor ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Coronary Reserve ◽  
Osmotic Pumps ◽  
Sprague Dawley Rats

We tested the hypothesis that chronically reducing the heart rate in infarcted middle-aged rats using ivabradine (IVA) would induce arteriolar growth and attenuate perivascular collagen and, thereby, improve maximal perfusion and coronary reserve in the surviving myocardium. Myocardial infarction (MI) was induced in 12-mo-old male Sprague-Dawley rats, which were then treated with either IVA (10.5 mg·kg−1·day−1; MI + IVA) or placebo (MI) via intraperitoneal osmotic pumps for 4 wk. Four weeks of IVA treatment limited the increase in left ventricular end-diastolic pressure and the decrease in ejection fraction but did not affect the size of the infarct, the magnitude of myocyte hypertrophy, or the degree of arteriolar and capillary growth. However, treatment reduced interstitial and periarteriolar collagen in the surviving myocardium of MI + IVA rats. The reduced periarteriolar collagen content was associated with improvement in maximal myocardial perfusion and coronary reserve. Although the rates of proliferation of periarteriolar fibroblasts were similar in the MI and MI + IVA groups, the expression levels of the AT1 receptor and transforming growth factor (TGF)-β1 in the myocardium, as well as the plasma level of the ANG II peptide, were lower in treated rats 14 days after MI. Therefore, our data reveal that improved maximal myocardial perfusion and coronary reserve in MI + IVA rats are most likely the result of reduced periarteriolar collagen rather than enhanced arteriolar growth.

scholarly journals Lack of protective effect of autotransplanted splenic tissue to pneumococcal challenge

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 475-478
Author(s):  
AD Schwartz ◽  
JF Goldthorn ◽  
JA Winkelstein ◽  
AJ Swift
Keyword(s):  
Animal Model ◽  
Splenic Tissue ◽  
Immune Functions ◽  
Sprague Dawley ◽  
Experimental Animals ◽  
Susceptibility To Infection ◽  
Normal Spleen ◽  
Sprague Dawley Rats ◽  
Encapsulated Bacteria ◽  
Increased Susceptibility

Studies in animals and clinical experience in patients have demonstrated that splenectomy may lead to an increased susceptibility to infection. The infections are usually caused by encapsulated bacteria such as penumococcus. It has been shown in a variety of experimental animals that autotransplanted splenic tissue is capable of regenerating into implants that are microscopically indistinguishable from normal spleen and of restoring a number of normal splenic functions. The response to intravenous challenge with Streptococcus pneumoniae, type 25, was therefore studied in control, asplenic, and autotransplanted Sprague-Dawley rats. Despite previous observations that a number of immune functions can be restored in this animal model by autotransplanted splenic tissue, the present study indicates that splenic tissue autotransplants do not restore the ability to resist intravenous pneumococcal challenge.

The Correlations Between Walking Analysis Parameters and Q1–Q4 Angles in the Experimental Animal Model of Sciatic Nerve Injury

2018 ◽  
Vol 24 (8) ◽  
pp. 6245-6248
Author(s):  
Ria Margiana ◽  
Renindra Ananda Aman ◽  
Jeanne Adiwinata Pawitan ◽  
Ahmad Aulia Jusuf ◽  
Nurhadi Ibrahim ◽  
...  
Keyword(s):  
Strongly Correlated ◽  
Spearman Correlation ◽  
Sprague Dawley ◽  
Functional Index ◽  
Experimental Animals ◽  
Sprague Dawley Rats ◽  
Different Color ◽  
Sciatic Functional Index ◽  
Ethics Commission ◽  
Medium Correlation

In the study conducted by Margiana et al., 2015, it has been known that the angle parameters around the point which acts as the meeting point of the lines between the heel and the third fingertip and between finger one and finger five (Q1, Q2, Q3, and Q4) are strongly correlated with Sciatic Functional Index (SFI), Tibial Functional Index (TFI) and Peroneal Functional Index (PFI) in experimental animals with normal walking function, however, whether these parameters can be used in cases of injury is unknown. This study aimed to prove that Q1, Q2, Q3, and Q4 are correlated with SFI, TFI and PFI. This experimental study used 36 Sprague-Dawley rats as the experimental animals that had been approved by the FKUI Ethics Commission. The Seddon 5 classification was done on the rats with end-to-end suture. The rats were allowed to walk in a hallway and different color inks had firstly been given on each rat’s paws. After the formation of foot prints, the measurement of all parameters was made. The Spearman correlation (SPSS 23) analysis showed that there were correlations between SFI, TFI, PFI and Q1, Q2, Q3 and Q4. The correlation coefficient range (r) were categorized as medium correlation. The conclusion of the research that has been conducted is that there are significant correlations between Q1, Q2, Q3, and Q4 with SFI. Thus, Q1, Q2, Q3, and Q4 can be used as one of the predictors of walking function.

scholarly journals Nitric oxide and carbon monoxide antagonize TGF-β through ligand-independent internalization of TβR1/ALK5

2014 ◽  
Vol 307 (6) ◽  
pp. F727-F735 ◽  
Author(s):  
Michael B. Hovater ◽  
Wei-Zhong Ying ◽  
Anupam Agarwal ◽  
Paul W. Sanders
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Cellular Response ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Surface Expression ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Β Receptor ◽  
Dynamin 2

Transforming growth factor (TGF)-β plays a central role in vascular homeostasis and in the pathology of vascular disease. There is a growing appreciation for the role of nitric oxide (NO) and carbon monoxide (CO) as highly diffusible, bioactive signaling molecules in the vasculature. We hypothesized that both NO and CO increase endocytosis of TGF-β receptor type 1 (TβR1) in vascular smooth muscle cells (VSMCs) through activation of dynamin-2, shielding cells from the effects of circulating TGF-β. In this study, primary cultures of VSMCs from Sprague-Dawley rats were treated with NO-releasing molecule 3 (a NO chemical donor), CO-releasing molecule 2 (a CO chemical donor), or control. NO and CO stimulated dynamin-2 activation in VSMCs. NO and CO promoted time- and dose-dependent endocytosis of TβR1. By decreasing TβR1 surface expression through this dynamin-2-dependent process, NO and CO diminished the effects of TGF-β on VSMCs. These findings help explain an important mechanism by which NO and CO signal in the vasculature by decreasing surface expression of TβR1 and the cellular response to TGF-β.

Curcumin and Saikosaponin A Inhibit Chemical-Induced Liver Inflammation and Fibrosis in Rats

2010 ◽  
Vol 38 (01) ◽  
pp. 99-111 ◽  
Author(s):  
Shu-Ju Wu ◽  
Ka-Wai Tam ◽  
Ya-Hui Tsai ◽  
Chun-Chao Chang ◽  
Jane C.-J. Chao
Keyword(s):  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Transforming Growth Factor Β1 ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Histopathological Results ◽  
Necrosis Factor ◽  
Saikosaponin A

Curcumin and saikosaponin A as antioxidants improve antioxidant status. This study investigated the anti-inflammatory and antifibrotic actions of curcumin and saikosaponin A on CCl4 -induced liver damage. Sprague-Dawley rats were randomly divided into control, CCl4 , CCl4+ curcumin (0.005%; CU), CCl4 + saikosaponin A (0.004%; SS), and CCl4 + curcumin + saikosaponin A (0.005% + 0.004%; CU + SS) groups. Carbon tetrachloride (40% in olive oil) at a dose of 0.75 ml/kg was injected intraperitoneally once a week. Curcumin and saikosaponin A were supplemented alone or in combination with diet 1 week before CCl4 injection for 8 weeks. After 8-week supplementation, histopathological results showed hepatic collagen deposition was significantly reduced in the CU and SS groups, and activated nuclear factor-κ B expression induced by CCl4 in the liver was significantly inhibited by curcumin and/or saikosaponin A. Hepatic proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 were significantly inhibited, and anti-inflammatory cytokine interleukin-10 was significantly increased by supplementation with curcumin and/or saikosaponin A. Additionally, curcumin and/or saikosaponin A significantly reduced the increased levels of hepatic transforming growth factor-β1 and hydroxyproline after CCl4 treatment. Therefore, supplementation with curcumin and/or saikosaponin A suppress inflammation and fibrogenesis in rats with CCl4 -induced liver injury. However, the combination has no additive effects on anti-inflammation and antifibrosis.

rhCygb reverses bleomycin-induced established pulmonary fibrosis in rats

2020 ◽  
Author(s):  
Li Zhen ◽  
Lin Zhongshun ◽  
Wang Ping ◽  
Wenqi Dong
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Volume Fraction ◽  
Serum Levels ◽  
Sprague Dawley ◽  
Type Iv ◽  
Animal Disease Models ◽  
Sprague Dawley Rats ◽  
Liver And Kidney ◽  
Serial Serum

Abstract PurposeRecombinant human cytoglobin (rhCygb) has been demonstrated to anti-inflammation, anti-oxidation, anti-fibrosis in liver and kidney in animal disease models. However, the effect of rhCygb on the progression of pulmonary fibrosis is still unclear. The aim of this study was to investigate the therapeutic effect of rhCygb in the bleomycin (BLM)-induced pulmonary fibrosis rats.MethodsWe tested whether rhCygb would reverse lung fibrosis (at day 28 and 56) in Sprague-Dawley rats treated with bleomycin. Bleomycin (5mg/kg) resulted in fibrosis by CT and serum measurement at day 7. Effects of rhCygb treatment on morphological and CT imaging of the lung, as well as serial serum levels of biomarkers with progressive lung fibrosis were tested at day 28 and 56.ResultsIn BLM-treated rats (7 days), the well-established lung fibrosis was evidence by changes in rat lungs with CT images and serum levels of hyaluronic acid (HA), laminin (LN), procollagen III N-terminal peptide (PIIINP) and type IV collagen (IVC).After treatment with rhCygb for 49 days, we found significantly decreasing in HA, LN, PIIINP and IVC levels almost to controls. Hydroxyproline (HYP) , CT mean lung density（MLD）and Masson collage volume fraction (CVF) were also significantly reduced. Furthermore, CT MLD positively correlated with serum levels of HA, LN, PIIINP, IVC, and HYP, and especially with CVF.ConclusionrhCygb may be a new potential medicine for reversing lung fibrosis in the future.

scholarly journals Determination of Effect on Cutaneous Wound Healing of Ozonated Hazelnut Oil

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1537
Author(s):  
Sibel Bayil Oğuzkan ◽  
Salih Tunç Kaya ◽  
Aziz Cesur ◽  
Bora Karagül ◽  
Serpil Uğraş ◽  
...  
Keyword(s):  
Wound Healing ◽  
Digital Camera ◽  
Dorsal Surface ◽  
Hazelnut Oil ◽  
Sprague Dawley ◽  
Experimental Animals ◽  
Sprague Dawley Rats ◽  
Package Program ◽  
The Stability ◽  
Marked Area

In this study, the wound healing effect of ozonated hazelnut oil was investigated on 54 male Sprague-Dawley rats. 7 experimental groups were designed. A circular area with a diameter of approximately 2 cm on dorsal surface was drawn using a coin and full thickness of the marked area was cut approximately 3 cm away from the ears by sterile scissors and forceps. All oils were daily applied on wound surface of experimental animals in volume of 0.2 mLduring 15 days. In this study, statistical analysis of the data was performed using the SPSS 22.0 package program. Wounds of all experimental animals were photographed by a digital camera on days 0, 3, 6, 12 and 15 after wounding. Ozonated oil treated wounds had significantly higher than the other groups on the day 3 after wounding. There is a quantitatively healing is determined on 3 day on rats. It has been observed in the stability period that ozonated oils must be stored at a temperature below 4 °C. Vitamin E should be added as an additive in the medical use of ozonated hazelnut oil in wound healing.

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