Scleroderma (SSc) is a chronic disease characterized by the overexpression of Extracellular Matrix (ECM) Proteins. Scleroderma disease can further develop into a fibrotic condition that causes deformation of the lungs and other internal organs (Song et al., 2011). The most important players in the development of SSc are myofibroblast cells and it is uncontrolled myofibroblast production of ECM proteins during healing process what differentiates SSc from normal healing processes (Del Galdo et al., 2008). In SSc fibroblasts, overproduction of proteins such as collagen, fibronectin, and glycosoaminoglycans has been observed as well as other pro-fibrotic cytokines (Atamas et al., 2003). The initial onset or origin of the disease is not clear …show more content…
In another study, Wang et al. (2006) found a reduction of Cav-1 in lung tissue of Idiopathic Pulmonary Fibrosis patients (IPF), which is a type of fibrotic disease. Cav-1 is one of three known to date Caveolin molecules and is known to regulate several physiological processes such as membrane trafficking, endocytosis, and signal transduction in cell proliferation and apoptosis (Wang et al., 2006). In addition to this, Cav-1 has been shown to play an important role in the regulation of ECM protein production via regulation of TGF-β receptor degradation (Del Galdo et al., 2008). TGF-β is a potent pro-fibrotic cytokine that binds to TGF-β receptor and has also been attributed to cause changes in Fibroblasts phenotype resulting in selection of fibroblasts resistant to apoptosis (Atamas et al., …show more content…
CXCR-4 receptor plays a major role in migration of cells towards the lungs. In patients with ILD, lung injury causes the upregulation of chemoattractant SDF-1 and monocytes with upregulated CXCR-4 follow SDF-1 concentration gradient and accumulate in lung tissue (Tourkina et al., 2011). This phenomenon is of great importance because monocytes serve as precursors of fibrocytes (Bucala, 1994). In the present study, a model of SSc disease was recreated in mice in order to observe any differences in Cav-1 and CXCR-4 expression between bleomycin treated mice bone marrow (BM) cells versus a control group and how these changes affect the migration rate of the BM cells towards SDF-1 chemoattractant. Additionally, analysis in the percentage of Fibrocyte population in lung tissue was done in control and experimental group mice in order to observe if the possible hypermigration of cells towards SDF-1 is associated with a greater percentage of Fibrocytes present in lung tissue of bleomycin treated
Margination and adhesion to the endothelium, in which accumulation of leukocytes occurs along the endothelial wall for adhesion. Afterward, these adhesions cause the separation of endothelial cells, allowing the leukocytes to extend and Transmigrate through the vessel walls. Followed by the response of chemical mediators(chemotaxis) that influence cell migration via an energy directed process which triggers the activation of Phagocytosis, in which monocytes, neutrophils, and tissue macrophages are activated to engulf and degrade cellular debris and
Fibrodysplasia ossificans progressiva also known as FOP is a one of the rarest, most disabling genetic bone conditions known to medicine. FOP causes muscles, tendons, ligaments, and other connective tissues to turn in to bone. Movement becomes limited in the affected areas of the body. People with FOP typically have malformed toes at birth, meaning the big toe is typically shorter than normal and abnormally turned outward in a position called a valgus deviation. Symptoms of FOP start to show up in early childhood. Most people with FOP develop painful tumor-like swellings also known as fibrous nodules. The fibrous nodules are visible on the neck, shoulders, and back.
Marfan syndrome (MFS) is known as an autosomal dominant hereditary disorder of connective tissue. Connective tissue helps support all parts of the body. It also helps control how the body grows and develops. Principal manifestations involve the ocular, skeletal, and cardiovascular systems. MFS is caused by mutations in the glycoprotein gene fibrillin-1 (FBN1) which is located on chromosome 15(Marcheix, 2008). There are many mutations that can cause Marfan Syndrome, but most common are missense in that they are single-nucleotide changes that result in the substitution of a single letter that leads to a single amino acid change in the protein. The change in the amino acid alters the shape of the fibrillin proteins. The irregularly-shaped protein then assembles into irregularly shaped microfibrils. Fibrillin is a major element of microfibrils, which store a protein called transforming growth factor beta (TGF-β), a critical growth factor. TGF-β helps control the proliferation of cells, cell differentiation, cell movement, and apoptosis. Microfibrils help regulate the availability of TGF-β, which is deactivated when stored in microfibrils and activated when released. The increase in TGF-β and abnormalities involving microfibrils causes problems in connective tissues throughout the body such as malformations and disfigurements of the ligaments, spinal dura, lens zonules, and lung airways(Marcheix, 2008). The heart is also greatly negatively impacted through a weakening of the aortic wall, progressive aortic dilatation or aortic disjointing can occur because of strain caused by left ventricular contractions.
Emphysema’s target is the lungs. The inflammation caused by emphysema damages the alveoli, or air sacs. Over time, the air sacs lose their elasticity, no longer able to expand and detract like your favorite Thanksgiving elastic waist band pants. After so many Thanksgiving dinners, the elastic fibers break, and fai...
...on and forms an inhibitory complex with caveolin-1 leads to decrease in activity of enzyme in the cells. Transcription of Cav-1 gene is regulated by cholesterol responsive elements. Exposure of fibroblast and endothelial cells to free cholesterol and LDL Cholesterol was found to up regulate Cav-1 expression. Ca+2 mobilizing agents cause disinhibiton of e NOS by promoting Ca+2/Calmodulin triggered dissociation of Cav-1.
Cystic Fibrosis (CF) is a very common, potentially life threatening condition. The disease is caused by inheritance, and affects the exocrine glands of the patient. Cystic fibrosis is found primarily among Caucasians and those of European descent. Those diagnosed with Cystic Fibrosis battle daily to perform simple tasks, such as breathing, as the mucus in their bodies thickens immensely. This mucus will potentially accumulate in the patient’s vital organs, such as the lungs, pancreas, and intestines. One can determine if he/she has cystic fibrosis by analyzing certain symptoms. Cystic Fibrosis can be diagnosed according to the symptoms the patient shows, and can be treated through specific types of treatments, such as gene therapy.
Marfan syndrome is an autosomal dominant disorder resulting from mutations in the gene fibrillin-1 (FBN1) found on chromosome 15 (McKusick V, O'Neill M, 2013). At least 140 different mutations of this gene have been recorded since 2008 (Frey R, Lutwick L, 2009). The FBN1 gene regulates the manufacturing of the fibrillin-1 protein that assists in constructing fibrous filaments which are present in portions of the fibers in connective tissue (Frey R, Lutwick L, 2009). Those filaments manage the discharge of growth factors or protein molecules which prompt the reproduction and growth of cells (Frey R, Lutwick L, 2009). In healthy individuals, the filaments discharge growth factors at the right moment but those who have Marfan syndrome are faced with the dilemma of growth factors being discharged too soon. The early release of growth factors results in fragile connective tissue and the uncommonly lengthy limbs of those with the disorder.
The sarcomere is found in structures called myofibrils which make up skeletal muscle fibres. Within the sarcomere there are various different proteins. One of the most significant, myosin is found in the thick filaments of the sarcomere. Although both cells contain myosin, it is important to highlight that smooth muscle cells contain a much lower percentage of myosin compared to skeletal muscle cells. Despite this, myosin filaments in smooth muscle cells bind to actin filaments in a manner similar to that in skeletal muscle cells; although there are some differences. For instance, myosin filaments in smooth muscle cells are saturated with myosin heads so that myosin can glide over bound actin filaments over longer distances, enabling smooth muscle cells to stretch further, whilst in skeleta...
Cystic Fibrosis is an autosomal recessive condition with roughly 1 in 30 Americans being carriers and 30,000 having the disease itself [1]. Its cause, generally speaking, is a mutation with a protein known as Cystic Fibrosis Transmembrane Conductance Regulator (CFTR.) Normally the CFTR protein is folded with the help of chaperone proteins, checked for mutaions by the endoplasmic reticulum and then moved to the apical surface of epithetical cells where it channels chloride ions out of epithelial cells and into mucus membranes [2]. Water then follows the chloride ions via simple osmosis allowing for a “less thick” mucus membrane. CFTR, however, is an immensely complicated protein with many folding steps and 1000s of mutations. The most common mutation is known as ΔF508 (deletion of a phenylalanine at residue 508) which accounts for roughly 70% of mutations worldwide [3]. There are a few other common mutations such as G551D and V232D [2].
The gene is found on the seventh chromosome in humans and contains 27 DNA sequences encoding 1,480 amino acids (Genetics). They found that the genetic change of this gene occurs through various mutations in the Cystic Fibrosis transmembrance conductance regulator or CTFR gene. Today 1,200 mutations are so far known. However, 70% of cystic fibrosis cases are caused by a single mutation, this mutation causes a deletion an amino acid at position 508 in the CTFR gene (Genetics). Once deleted the CTFR protein folds improperly and breaks down shortly after being made. Ultimately, every mutation affects the genes normal function as a channel protein. The CTFR gene crosses the membrane of many cell types, which is why the disease is referred to as a multisystem condition (Cystic). These cells are in charge of producing sweat, saliva, and tears. Its target is chloride ions whose movement in and out of the cell regulates the concentration of water in the tissue (Cystic). The movement of water is so crucial because it is responsible for keeping the mucus in our bodies thin and freely moving. So when mutations occur to this channel protein the flow of chloride ions is disrupted ultimately leading to the build up of thick damaging mucus associated with the disease
Husain, A., (2010), The Lung, Robbins and Cotran Pathologic Basis of Disease, pp. 677-737, Philadelphia: Saunders Elsevier
Qvar is a common known medicine for asthma that helps control asthma and its symptoms but doesn’t necessarily cure it. The medicine in Qvar was designed to reach large and small airway inflammation. In our bodies lungs are made up of large and small airways. Chronic lung inflammation caused by asthma affects both the large and small airways. If this is left unattended, damage c...
(Järvinen, Järvinen, Kääriäinen, Kalimo, Järvinen, 2005) (Järvinen, 2014). The destruction phase begins with torn or ruptured myofibers that have become necrotized of only a few hours. The necrosis of the entire myofiber is prevented by a “Fire door” or contraction banded that forms around the rupture and is sealed by new sarcolemma. The torn myofibers contract leaving a gap between the torn ends of the myofiber. This gap is filled with blood, giving inflammatory cells that have been activated by the injury, direct access to the ruptured myofibers. Chemotactic signals including growth factors and cytokines are released by macrophages and fibroblast and are activated in the extracellular matrix for the circulating inflammatory cells (Järvinen, 2014) (Järvinen, 2005).The repair phases begins as macrophage cells continue a process call phagocytosis to remove the necrotized tissues while committed satellite cells begin to differentiate into myoblast. Undifferentiated satellite cells begin to proliferate within 24 hours and contribute to the production of myoblasts. These myoblasts form together to create myotubes which regenerate myofibers. Within 5 to 6 days the necrotized myofiber will be replaced with the regenerating myofiber, which connects with the connective scar tissue between the two ruptured ends of the myofiber. The remodeling phases begins as new
Pulmonary Fibrosis is a condition where the lung tissue becomes thick and scarred. The thickening and scarring of the lungs makes it hard for the oxygen supply to be delivered throughout the body. The scarring can be caused by many different factors, but it is hard for doctors to figure out exactly what caused the onset of this disease. The damage caused by this disease cannot be repaired. Pulmonary Fibrosis usually affects the age group of forty to seventy years old. Men are more likely to develop this disease, but women can also get this disease. Pulmonary Fibrosis is not a transmittable disease. Little is actually known about how the disease develops. There seems to be a genetic connection and environmental factors that cause the disease to develop.
Vijayan, V. K. (2013). Chronic obstructive pulmonary disease. Indian Journal Of Medical Research, 137(2), 251-269.