scholarly journals Modeling of bacterial lipopolysaccharide-induced endometritis in rats and the possibility of its therapy using plasma enriched with soluble platelet factors

Author(s):  
M. Potapnev ◽  
K. Pavlov ◽  
O. Doronina ◽  
T. Metelitsa ◽  
E. Anfinogenova ◽  
...  

We presents results of a study on endometritis modeling in rats with double intravaginal administration of bacterial lipopolysaccharide (LPS). The established endometrial inflammatory process was accompanied by a decrease in the weight of animals, an increase in the weight of the uterus, neutrophilic infiltration, edema, and overexpression of cyclooxygenase in endometrium on 30-45 days after the start of endometritis induction. Local intravaginal use of plasma enriched with soluble platelet factors/platelet-rich plasma (PORFT/PRP) caused a decrease in the intensity of the inflammatory process and the rate of neutrophil infiltration of the endometrium, a decrease in the intensity of cyclooxygenase, interleukin-6 and transforming growth factor-β expression, and an increase in the body weight of animals. The conclusion was made on the possibility of creating model of endometritis in rats by double administration of LPS and the ability of local administration of PORFT/PRP to have a therapeutic effect on the inflammatory process in the endometrium.

2018 ◽  
Vol 19 (11) ◽  
pp. 3672 ◽  
Author(s):  
Yutaro Tsubakihara ◽  
Aristidis Moustakas

Metastasis of tumor cells from primary sites of malignancy to neighboring stromal tissue or distant localities entails in several instances, but not in every case, the epithelial-mesenchymal transition (EMT). EMT weakens the strong adhesion forces between differentiated epithelial cells so that carcinoma cells can achieve solitary or collective motility, which makes the EMT an intuitive mechanism for the initiation of tumor metastasis. EMT initiates after primary oncogenic events lead to secondary secretion of cytokines. The interaction between tumor-secreted cytokines and oncogenic stimuli facilitates EMT progression. A classic case of this mechanism is the cooperation between oncogenic Ras and the transforming growth factor β (TGFβ). The power of TGFβ to mediate EMT during metastasis depends on versatile signaling crosstalk and on the regulation of successive waves of expression of many other cytokines and the progressive remodeling of the extracellular matrix that facilitates motility through basement membranes. Since metastasis involves many organs in the body, whereas EMT affects carcinoma cell differentiation locally, it has frequently been debated whether EMT truly contributes to metastasis. Despite controversies, studies of circulating tumor cells, studies of acquired chemoresistance by metastatic cells, and several (but not all) metastatic animal models, support a link between EMT and metastasis, with TGFβ, often being a common denominator in this link. This article aims at discussing mechanistic cases where TGFβ signaling and EMT facilitate tumor cell dissemination.


2003 ◽  
Vol 12 (5) ◽  
pp. 509-518 ◽  
Author(s):  
Masaki Yazawa ◽  
Hisao Ogata ◽  
Tatsuo Nakajima ◽  
Taisuke Mori ◽  
Naohide Watanabe ◽  
...  

Platelets, which contain many growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β), are being used in clinical applications as platelet-rich plasma (PRP). Only a few studies, however, have been conducted on the growth factors present in PRP and on the clinical applications using the drug delivery system (DDS). For the purpose of clinical application, we first modified the PRP preparation method and assessed the amounts of growth factors contained in the human platelet concentrates. Furthermore, we assessed fibrin glue as a DDS of platelet concentrates. Platelet precipitations were made by twice centrifuging human whole blood. The precipitated platelet was resuspended to yield the platelet concentrates. The growth factor concentrations were measured. Fibrin glue sheets containing this platelet concentrate were implanted in rabbit pinna and samples were obtained for immunostaining (anti-PDGF antibody) to assess the use of PRP over time using the fibrin glue as the DDS. The mean concentration of growth factors present in the platelet concentrates was three times or greater than that of conventional PRP. Furthermore, the results indicated that when the platelet concentrate was used with fibrin glue as a carrier, the contents were released over a period of about 1 week. This raises the possibility that this system may be useful in clinical applications.


2021 ◽  
Vol 118 (33) ◽  
pp. e2111401118
Author(s):  
Yewei Liu ◽  
Adam Lehar ◽  
Renata Rydzik ◽  
Harshpreet Chandok ◽  
Yun-Sil Lee ◽  
...  

Skeletal muscle and bone homeostasis are regulated by members of the myostatin/GDF-11/activin branch of the transforming growth factor-β superfamily, which share many regulatory components, including inhibitory extracellular binding proteins and receptors that mediate signaling. Here, we present the results of genetic studies demonstrating a critical role for the binding protein follistatin (FST) in regulating both skeletal muscle and bone. Using an allelic series corresponding to varying expression levels of endogenous Fst, we show that FST acts in an exquisitely dose-dependent manner to regulate both muscle mass and bone density. Moreover, by employing a genetic strategy to target Fst expression only in the posterior (caudal) region of the animal, we show that the effects of Fst loss are mostly restricted to the posterior region, implying that locally produced FST plays a much more important role than circulating FST with respect to regulation of muscle and bone. Finally, we show that targeting receptors for these ligands specifically in osteoblasts leads to dramatic increases in bone mass, with trabecular bone volume fraction being increased by 12- to 13-fold and bone mineral density being increased by 8- to 9-fold in humeri, femurs, and lumbar vertebrae. These findings demonstrate that bone, like muscle, has an enormous inherent capacity for growth that is normally kept in check by this signaling system and suggest that the extent to which this regulatory mechanism may be used throughout the body to regulate tissue mass may be more significant than previously appreciated.


2018 ◽  
Vol 44 (1) ◽  
pp. 32-40
Author(s):  
Binboğa Sinan ◽  
Kasapoğlu Pınar ◽  
Binboğa Elif ◽  
Cikot Murat ◽  
Baytekin Fırat ◽  
...  

Abstract Background Autologous platelet rich plasma (PRP) is the platelet concentration obtained from thrombocytes in the plasma. During the healing process, the platelets are activated and then release the granules which stimulate the inflammatory cascade and healing process. Platelet derived growth factor, vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ), epidermal growth factor (EGF) and fibroblast growth factor (FGF) are valuable markers used for cell regeneration. The aim of this study was to investigate the potential effects of PRP treatment on the neomucosa formation, a potential technique for increasing the intestinal surface area in patients with short bowel syndrome (SBS). Materials and methods Thirty-two male Wistar-Hannover rats were divided into: sham, control, PRP-treated and last group for PRP preparation (n=8). Plasma levels of VEGF, TGFβ, EGF and FGF were quantified by ELISA. En-bloc resection of anastomotic part was performed and stained with hematoxylin-eosin. Results VEGF, FGF, TGFβ and EGF levels were found significantly increased in PRP-treated group compared to others (p<0.001). Neomucosa formation was observed in experimental groups but the area increased significantly in PRP group, compared to other groups (p<0.001). Conclusion PRP therapy in gastrointestinal anastomoses is truly beneficial and surgically applicable treatment in SBS patients.


2017 ◽  
Vol 26 (3) ◽  
pp. 381-394 ◽  
Author(s):  
Shiying Li ◽  
Xiaosong Gu ◽  
Sheng Yi

Transforming growth factor-β (TGF-β) belongs to a group of pleiotropic cytokines that are involved in a variety of biological processes, such as inflammation and immune reactions, cellular phenotype transition, extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition. TGF-β is widely distributed throughout the body, including the nervous system. Following injury to the nervous system, TGF-β regulates the behavior of neurons and glial cells and thus mediates the regenerative process. In the current article, we reviewed the production, activation, as well as the signaling pathway of TGF-β. We also described altered expression patterns of TGF-β in the nervous system after nerve injury and the regulatory effects of TGF-β on nerve repair and regeneration in many aspects, including inflammation and immune response, phenotypic modulation of neural cells, neurite outgrowth, scar formation, and modulation of neurotrophic factors. The diverse biological actions of TGF-β suggest that it may become a potential therapeutic target for the treatment of nerve injury and regeneration.


2009 ◽  
Vol 17 (3-4) ◽  
pp. 61-64 ◽  
Author(s):  
Vesna Ivanovic

Transforming growth factor-? (TGF-?), an extensively investigated cytokine, plays a very important role in promoting the spread of cancers in the body, and can play a direct role in facilitating metastasis. Consequently, TGF-? is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis. Therefore, in clinical scenarios involving increased TGF-? activity, attempts to decrease or abrogate TGF-? signaling could be used as a therapy for advanced or metastatic disease. It follows that TGF-? signaling offers an attractive target for cancer therapy. Several anti-TGF-? approaches, such as TGF-? antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-? type 1 receptor kinase, have shown great promise in the preclinical studies. These studies, coupled with progressing clinical trials indicate that inhibition of TGF-? signaling may be indeed a viable option to cancer therapy. This review summarizes the TGF-? biology, screening cancer patients for anti-TGF-? therapy, and several strategies targeted against TGF-? signaling for cancer therapy. The next several years promise to improve our understanding of approaching cancer therapy by further evaluation of TGF-? signaling inhibitors for clinical efficacy. The complexity of TGF-? biology guarantees that many surprises lie ahead.


Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 341
Author(s):  
Kimiko Takebayashi-Suzuki ◽  
Atsushi Suzuki

During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal–ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior–posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos.


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