transforming-growth-factor-beta and Collagen-Diseases

Systemic sclerosis is a complex multi-systemic disease with a mostly unresolved pathogenesis. Following an inflammatory reaction, overproduction of collagen and other extra-cellular matrix components leads to a characteristic fibrosis. It remains unclear why this overproduction by fibroblasts and myofibroblasts occurs. Micro-vascular disturbances and endothelial cells, as well as immunomodulation and inflammation are central factors. Besides intrinsic influences, such as genetic polymorphisms, multiple mediators with fibrotic effects such as Platelet Derived Growth Factor, Transforming Growth Factor-beta and Connective Tissue Growth Factor have been characterized. These have become targets for innovative therapeutic strategies that might lead to specific treatments for systemic sclerosis.

Topics: Animals; Antibodies, Antinuclear; Autoantibodies; Collagen Diseases; Disease Models, Animal; Endothelial Cells; Extracellular Matrix; Fibroblasts; Fibrosis; Humans; Mice; Platelet-Derived Growth Factor; Scleroderma, Systemic; Skin; Transforming Growth Factor beta; Vasoconstriction

Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is characterized by a generalized submucosal fibrosis. The pathogenesis of the disease is not well established. Epidemiological evidences strongly indicate the association of the betel quid (BQ) habit and OSF. Various findings indicate the disease to be a consequence of disturbances in the homeostatic equilibrium between synthesis and degradation of extracellular matrix (ECM), wherein collagen forms a major component, thus can be considered as a collagen-metabolic disorder. Transforming growth factor-beta (TGF-beta) is a potent stimulator of production and deposition of the ECM. The objectives of this review are to highlight the molecular events involved in the overproduction of insoluble collagen and decreased degradation of collagen occurring via exposure to BQ and stimulation of the TGF-beta pathway, and elucidate the cell signaling that is involved in the etiopathogenesis of the disease process.

Topics: Areca; Collagen; Collagen Diseases; Humans; Oral Submucous Fibrosis; Signal Transduction; Transforming Growth Factor beta

The status of the patient's associated disease can generally affect the onset or healing of acquired reactive perforating collagenosis (ARPC). We treated eight cases of ARPC and noted that the patients had similar findings. However, it was not clear why ARPC developed in the patients with these diseases. Nevertheless, several factors related to the diseases associated with ARPC could affect the degeneration of collagen fibers or the production of dermal products. Some patients had diseases that were characterized by fibrosis and an increased amount of reticular fibers. Factors related to tissue remodeling might act not only in diseases associated with ARPC but also in ARPC itself.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Collagen; Collagen Diseases; Diabetes Mellitus, Type 2; Female; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Pulmonary Fibrosis; Reticulin; Skin Diseases; Transforming Growth Factor beta

Reactive perforating collagenosis (RPC) is a rare disorder characterized by the transepidermal elimination of altered collagen. The inherited form of RPC begins in early childhood, but acquired reactive perforating collagenosis (ARPC) begins in adult life. ARPC is associated with diabetes mellitus, renal disease, and malignancy. ARPC with lung fibrosis has not previously been reported in the literature, and the relationship between ARPC and lung fibrosis has not been studied. The etiological relationship between the two disorders appears to be uncertain. Although their association in this case could be due to chance, it may be due to the transforming growth factor beta abnormalities seen in both diseases. In this report, we describe a case of ARPC with lung fibrosis and propose an etiological association between the two diseases.

Topics: Collagen; Collagen Diseases; Elastic Tissue; Epidermis; Humans; Male; Middle Aged; Pulmonary Fibrosis; Skin Diseases, Papulosquamous; Transforming Growth Factor beta; Transforming Growth Factor beta1

Topics: Adult; Aged; Collagen Diseases; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Skin; Transforming Growth Factor beta; Transforming Growth Factor beta3

Collagen was studied by biochemical and immunohistochemical techniques and by in situ hybridization in four patients with lichen sclerosus et atrophicus (LSA). The solubility of collagen in acetic acid and pepsin was increased in the lesional skin of the LSA patients when compared with their non-affected skin or samples from control subjects, indicating that a marked proportion of the collagen was newly synthesized. Collagen synthesis was slightly increased in fibroblasts derived from the lesional skin of the LSA patients. In situ hybridization with human sequence-specific cDNAs to type I procollagen demonstrated active fibroblasts in lesional skin of LSA patients, further confirming a high level of collagen synthesis in LSA. Remarkably, active fibroblasts were not associated with inflammatory cell infiltrates noted in LSA skin nor did they express transforming growth factor beta(TGF beta 1). Our results indicate that despite the degeneration of connective tissue, there is an active regeneration process in LSA with significant collagen synthesis.

Topics: Aged; Blotting, Northern; Cells, Cultured; Collagen; Collagen Diseases; Female; Fibroblasts; Humans; Middle Aged; Nucleic Acid Hybridization; RNA, Messenger; Skin; Skin Diseases; Transforming Growth Factor beta