scholarly journals Impaired Lymphatic Drainage and Interstitial Inflammatory Stasis in Chronic Musculoskeletal and Idiopathic Pain Syndromes: Exploring a Novel Mechanism

2021 ◽  
Vol 2 ◽  
Author(s):  
Brian Tuckey ◽  
John Srbely ◽  
Grant Rigney ◽  
Meena Vythilingam ◽  
Jay Shah
Keyword(s):  
Inflammatory Mediators ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lymphatic Drainage ◽  
The Body ◽  
Vascular Perfusion ◽  
Feed Forward ◽  
Pain Syndromes ◽  
Pump Mechanism ◽  
Lymphatic Pathways

A normal functioning lymphatic pump mechanism and unimpaired venous drainage are required for the body to remove inflammatory mediators from the extracellular compartment. Impaired vascular perfusion and/or lymphatic drainage may result in the accumulation of inflammatory substances in the interstitium, creating continuous nociceptor activation and related pathophysiological states including central sensitization and neuroinflammation. We hypothesize that following trauma and/or immune responses, inflammatory mediators may become entrapped in the recently discovered interstitial, pre-lymphatic pathways and/or initial lymphatic vessels. The ensuing interstitial inflammatory stasis is a pathophysiological state, created by specific pro-inflammatory cytokine secretion including tumor necrosis factor alpha, interleukin 6, and interleukin 1b. These cytokines can disable the local lymphatic pump mechanism, impair vascular perfusion via sympathetic activation and, following transforming growth factor beta 1 expression, may lead to additional stasis through direct fascial compression of pre-lymphatic pathways. These mechanisms, when combined with other known pathophysiological processes, enable us to describe a persistent feed-forward loop capable of creating and maintaining chronic pain syndromes. The potential for concomitant visceral and/or vascular dysfunction, initiated and maintained by the same feed-forward inflammatory mechanism, is also described.

The emerging role of transforming growth factor-beta in kidney diseases

1994 ◽  
Vol 266 (6) ◽  
pp. F829-F842 ◽  
Author(s):  
K. Sharma ◽  
F. N. Ziyadeh
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cellular Response ◽  
Transforming Growth Factor ◽  
The Body ◽  
Special Focus ◽  
Tgf Beta ◽  
Growth Factor Beta

Transforming growth factor-beta (TGF-beta) is a prototypical multifunctional cytokine, with growth being only one of its many functions. Its receptors and actions are germane to almost every cell in the body involved in tissue injury and repair, and its effects are best understood in the context of a cellular response to a changing environment. The broad areas in which TGF-beta plays a crucial role include cell proliferation and extracellular matrix production. TGF-beta is a key regulatory molecule in the control of the activity of fibroblasts and has been implicated in several disease states characterized by excessive fibrosis. In the kidney, TGF-beta promotes tubuloepithelial cell hypertrophy and regulates the glomerular production of almost every known molecule of the extracellular matrix, including collagens, fibronectin, tenascin, and proteoglycans, as well as the integrins that are the receptors for these molecules. Furthermore, TGF-beta blocks the destruction of newly synthesized extracellular matrix by upregulating the synthesis of protease inhibitors and downregulating the synthesis of matrix-degrading proteases such as stromelysin and collagenase. As will be discussed, there is a strong body of in vitro and in vivo evidence suggesting that persistent overproduction of TGF-beta 1 in glomeruli after the acute inflammatory stage of glomerulonephritis causes glomerulosclerosis. TGF-beta may also be important in a variety of other chronic renal disorders characterized by hypertrophy and sclerosis, such as diabetic nephropathy. In this review we will attempt to offer a basic understanding of the cellular and molecular biology of TGF-beta and its receptors, with special focus on the role of the TGF-beta system in the kidney during development, growth, and disease.

scholarly journals Dead muscle tissue promotes dystrophic calcification by lowering circulating TGF-β1 level

2020 ◽  
Vol 9 (11) ◽  
pp. 742-750
Author(s):  
La Li ◽  
Shiqi Xiang ◽  
Bing Wang ◽  
Hang Lin ◽  
Guorui Cao ◽  
...  
Keyword(s):  
Muscle Tissue ◽  
Transforming Growth Factor Beta ◽  
Muscle Injury ◽  
Transforming Growth Factor ◽  
Pathological Condition ◽  
The Body ◽  
Dystrophic Calcification ◽  
Mouse Muscle ◽  
Tgf Β1

Aims Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. Methods We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin. Results Our findings showed that the presence of devitalized muscle tissue could cause a systemic decrease in circulating transforming growth factor-beta 1 (TGF-β1), which promoted DC formation following muscle injury. We further demonstrated that suppression of TGF-β signalling promoted DC in vivo, and potentiated osteogenic differentiation of muscle-derived stromal cells in vitro. Conclusion Taken together, these findings suggest that TGF-β1 may play a protective role in dead muscle tissue-induced DC, which is relevant to understanding the pathogenesis of post-traumatic HO. Cite this article: Bone Joint Res 2020;9(11):742–750.

scholarly journals miR-191 is involved in renal dysfunction in arsenic-exposed populations by regulating inflammatory response caused by arsenic from burning arsenic-contaminated coal

2019 ◽  
Vol 39 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Y Xu ◽  
Z Zou ◽  
Y Liu ◽  
Q Wang ◽  
B Sun ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Renal Dysfunction ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Scientific Basis ◽  
The Body ◽  
Targeted Prevention ◽  
Necrosis Factor Alpha ◽  
Multiple Organs ◽  
Factor Alpha

Chronic exposure to arsenic may result in the manifestation of damage in multiple organs or systems of the body. Arsenic-induced renal dysfunction has been determined, but their pathogenesis has not been fully examined. In this study, we measured the expression levels of miR-191 in plasma, the contents of pro-inflammatory (interleukin (IL)-6 and tumor necrosis factor alpha) and anti-inflammatory (IL-2 and transforming growth factor beta) cytokines, and renal dysfunction indicators (blood urea nitrogen, blood creatinine, uric acid, and cystatin C) in serum from control and arsenic poisoning populations and analyzed the relationship between the miR-191, cytokines, and renal dysfunction indicators. The results clearly show the alteration of miR-191 expression was significantly associated with arsenic-induced renal dysfunction. Overall, the association of miR-191, inflammatory response and renal dysfunction, is clearly supported by the current findings. In other words, miR-191 is involved in renal dysfunction in exposed populations by regulating inflammatory response caused by coal-burning arsenic. The study provides a scientific basis for further studies of the causes of the arsenic-induced renal dysfunction, the biological role of miR-191, and targeted prevention strategies.

scholarly journals Control of body temperature and immune function in patients undergoing open surgery for gastric cancer

2018 ◽  
Vol 18 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Li Shao ◽  
Nannan Pang ◽  
Ping Yan ◽  
Fengju Jia ◽  
Qi Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Body Temperature ◽  
Immune Function ◽  
Transforming Growth Factor Beta ◽  
Open Surgery ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
The Body ◽  
Infection Rates ◽  
Infusion Fluids

The influence of mild perioperative hypothermia on the immune function and incidence of postoperative wound infections has been suggested, but the specific mechanism is unclear. This study aimed to analyze the body temperature, immune function, and wound infection rates in patients receiving open surgery for gastric cancer. Body temperature was controlled in each patient using one of four different methods: wrapping limbs, head and neck; insulated blankets; warming infusion fluids and insulated blankets; and warming fluids without insulated blankets. One hundred patients were randomly divided into four groups of 25 patients each, and every group received a different intraoperative treatment for maintaining normal body temperature. Nasopharyngeal and rectal temperatures, transforming growth factor beta (TGF-β), interleukin 10 (IL-10) levels, and cluster of differentiation (CD)3+T and CD4+/CD25+ regulatory T cell (Treg) counts were measured before surgery and at 2 and 4 hours postoperatively. Patients were evaluated at one week after surgery for signs of infection. Intraoperative body temperature and measures of immune function varied significantly between the four groups, with the largest temperature changes observed in the group in which only the limbs were wrapped in cotton pads to control the body temperature. The lowest temperature change (i.e., close to normal temperature) and cytokine response after surgery were observed in the group in which infusion fluids and transfused blood (if needed) were heated to 37℃, peritoneal irrigation fluid was heated to 37℃, and an insulation blanket was heated to 39℃ and placed under the patient. No intergroup differences were found in the infection rates at one week after surgery. In conclusion, body temperature variation during surgery affects the immune function of patients, and maintaining body temperature close to normal results in the least variation of immune function.

scholarly journals Changes in profibrotic activity in cardiovascular diseases

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Ivaneta D Yoncheva ◽  
Denislav E Biserov ◽  
Maria N Negreva MD
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Disease Process ◽  
Tissue Growth ◽  
The Body ◽  
Collagen Molecule ◽  
Type Iii Collagen ◽  
Type I ◽  
Amino Terminal

The myocardium consists of several types of cells: cardiomyocytes, cardiac fibroblasts, endothelial cells and smooth muscle cells. Fibroblasts are cells of mesenchymal origin and are present in all tissues in the body. Cardiac damage can activate available CFBs, provoke transformation of endothelial or epithelial cells into fibroblasts, or induce the production of CFBs from hematopoietic cells and bone marrow. The change in ECM is a key point in the remodeling of the heart in response to the disease process. Disruption of the reticular structure of the ECM alters the connection between myocardial cells and blood vessels, thereby disrupting the structure and function of the heart muscle. Type I and III collagen fibrils are the predominant part of the ECM of the heart. They are synthesized as procollagen, which is converted to a mature collagen molecule. Procollagen type I propeptide (PICP), amino-terminal propeptide type I procollagen (PINP) and N terminal type III collagen peptide (PIIINP) are released in proportional amounts in the synthesis of collagen types I and III and can be used as serum markers for these processes. On the other hand the differentiation from CFBs to myoFB is supported by the transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), a number of cytokines in the ECM and others. The scientific community is faced with the question of which biomarkers to use to identify the early stages of development of cardiac fibrosis, as well as how to assess the degree of progression of this pathological process.

scholarly journals Microbiota Composition of Breast Milk from Women of Different Ethnicity from the Manawatu—Wanganui Region of New Zealand

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1756
Author(s):  
Christine A. Butts ◽  
Gunaranjan Paturi ◽  
Paul Blatchford ◽  
Kerry L. Bentley-Hewitt ◽  
Duncan I. Hedderley ◽  
...  
Keyword(s):  
Body Mass Index ◽  
New Zealand ◽  
Breast Milk ◽  
Body Mass ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fecal Microbiota ◽  
The Body ◽  
Pacific Island ◽  
Microbiota Composition

Human breastmilk components, the microbiota and immune modulatory proteins have vital roles in infant gut and immune development. In a population of breastfeeding women (n = 78) of different ethnicities (Asian, Māori and Pacific Island, New Zealand European) and their infants living in the Manawatu–Wanganui region of New Zealand, we examined the microbiota and immune modulatory proteins in the breast milk, and the fecal microbiota of mothers and infants. Breast milk and fecal samples were collected over a one-week period during the six to eight weeks postpartum. Breast milk microbiota differed between the ethnic groups. However, these differences had no influence on the infant’s gut microbiota composition. Based on the body mass index (BMI) classifications, the mother’s breast milk and fecal microbiota compositions were similar between normal, overweight and obese individuals, and their infant’s fecal microbiota composition also did not differ. The relative abundance of bacteria belonging to the Bacteroidetes phylum was higher in feces of infants born through vaginal delivery. However, the bacterial abundance of this phylum in the mother’s breast milk or feces was similar between women who delivered vaginally or by cesarean section. Several immune modulatory proteins including cytokines, growth factors, and immunoglobulin differed between the BMI and ethnicity groups. Transforming growth factor beta 1 and 2 (TGFβ1, TGFβ2) were present in higher concentrations in the milk from overweight mothers compared to those of normal weight. The TGFβ1 and soluble cluster of differentiation 14 (sCD14) concentrations were significantly higher in the breast milk from Māori and Pacific Island women compared with women from Asian and NZ European ethnicities. This study explores the relationship between ethnicity, body mass index, mode of baby delivery and the microbiota of infants and their mothers and their potential impact on infant health.

scholarly journals Insights into Bone Morphogenetic Protein—(BMP-) Signaling in Ocular Lens Biology and Pathology

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2604
Author(s):  
Daisy Y. Shu ◽  
Frank J. Lovicu
Keyword(s):  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Bmp Signaling ◽  
The Body ◽  
Ocular Lens ◽  
Mesenchymal Transition

Bone morphogenetic proteins (BMPs) are a diverse class of growth factors that belong to the transforming growth factor-beta (TGFβ) superfamily. Although originally discovered to possess osteogenic properties, BMPs have since been identified as critical regulators of many biological processes, including cell-fate determination, cell proliferation, differentiation and morphogenesis, throughout the body. In the ocular lens, BMPs are important in orchestrating fundamental developmental processes such as induction of lens morphogenesis, and specialized differentiation of its fiber cells. Moreover, BMPs have been reported to facilitate regeneration of the lens, as well as abrogate pathological processes such as TGFβ-induced epithelial-mesenchymal transition (EMT) and apoptosis. In this review, we summarize recent insights in this topic and discuss the complexities of BMP-signaling including the role of individual BMP ligands, receptors, extracellular antagonists and cross-talk between canonical and non-canonical BMP-signaling cascades in the lens. By understanding the molecular mechanisms underlying BMP activity, we can advance their potential therapeutic role in cataract prevention and lens regeneration.

scholarly journals Effect of seminal plasma or transforming growth factor on bovine endometrial cells

Reproduction ◽  
2019 ◽  
Vol 158 (6) ◽  
pp. 529-541 ◽  
Author(s):  
Jason A Rizo ◽  
Laila A Ibrahim ◽  
Paula C C Molinari ◽  
Bo R Harstine ◽  
Rachel L Piersanti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Seminal Plasma ◽  
Inflammatory Mediators ◽  
Transforming Growth Factor Beta ◽  
Artificial Insemination ◽  
Transforming Growth Factor ◽  
Bioactive Molecules ◽  
Endometrial Cells ◽  
Bovine Semen ◽  
Growth Factor Beta

Semen induces post-coital inflammation of the endometrium in several species. Post-coital inflammation is proposed to alter the endometrial environment of early pregnancy, mediate embryonic development and modulate the maternal immune response to pregnancy. In cattle, it is common for pregnancies to occur in the absence of whole semen due to the high utilization of artificial insemination. Here, we have utilized a cell culture system to characterize semen-induced expression of inflammatory mediators in bovine endometrial cells and test the efficacy of transforming growth factor beta as the active agent in mediating any such change. We hypothesize that seminal plasma-derived transforming growth factor beta increases the expression of inflammatory mediators in bovine endometrial cells. Initially, we describe a heat-labile cytotoxic effect of seminal plasma on BEND cells, and a moderate increase in IL1B and IL6 expression. In addition, we show that transforming growth factor beta is present in bovine semen and can increase the expression of endometrial IL6, whereas blocking transforming growth factor beta in semen ameliorates this effect. However, intra-uterine infusion of seminal plasma, sperm or transforming growth factor beta did not alter the endometrial expression of inflammatory mediators. We conclude that bovine semen can modulate endometrial gene expression in vitro, which is partially due to the presence of transforming growth factor beta. It is likely that additional, unidentified, bioactive molecules in semen can alter the endometrial environment. Characterizing bioactive molecules in bovine semen may lead to the development of additives to improve artificial insemination in domestic species.

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