1.
Transforming growth factor β1 (TGFβ1) in physiology and pathology.
Kajdaniuk, D, Marek, B, Borgiel-Marek, H, Kos-Kudła, B
Endokrynologia Polska. 2013;(5):384-96
Abstract
This review describes precisely the consequence of TGFβ1 prevalence in the organism, and its significant influence on physiological and pathophysiological processes. Organ and tissue distinctiveness hinder unambiguous characterisation of the cytokine. However, there are constant functions of TGFβ1 inducing no controversy: it participates in foetal development, control of cell growth and differentiation, induces fibrosis and scar formation (the process of 'wound healing'), causes the suppression of immune response, is involved in angiogenesis, the development of tumours, and inflammatory processes. Thus, TGFβ1 is a multifunctional cytokine. There are three fundamental directions of its activities: I. TGFβ1 regulates cell proliferation, growth, differentiation and cells movement. II. TGFβ1 has immunomodulatory effects. III. TGFβ1 has profibrogenic effects. TGFβ1 action can be local and systemic. This review describes TGFβ1 in pathology: colitis ulcerosa, Crohn's disease, coeliac disease, diabetic nephropathy, diabetic retinopathy and diabetic foot, pulmonary hypertension, and Alzheimer's disease. TGFβ1 and its receptors are also of interest to endocrinologists. Lack of TGFβ1-dependent growth control may result in oncogenesis: papillary, follicular and anaplastic thyroid cancers, prostate, breast and uterine cervical cancer, oesophagus, gastric, colorectal and liver cancers, NSCLC, and malignant melanoma. Excessive TGFβ1 activity is an integral part of the fibrotic processes occurring in the response to injury. An increased TGFβ1 expression has been observed in patients with pulmonary, kidney, and liver fibrosis. In chronic hepatitis, the prolonged stimulation of hepatic stellate cells being the result of chronic damage to hepatocytes results in the release of profibrogenic abundant factors such as TGFβ1 and leads to the development of liver cirrhosis. The results of experimental procedures and treatment known as anti-TGFβ1 strategy acting against the fibrosis in various tissues leads to hope regarding the use of anti-TGFβ1 strategy in clinical practice.
2.
Manipulating angiogenesis in medicine.
Carmeliet, P
Journal of internal medicine. 2004;(5):538-61
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Abstract
Blood vessels nourish organs with vital nutrients and oxygen and, thus, new vessels form when the embryo needs to grow or wounds are to heal. However, forming new blood vessels is a complex and delicate process, which, unfortunately, is often derailed. Thus, when insufficient vessels form, the tissue becomes ischaemic and stops to function adequately. Conversely, when vessels grow excessively, malignant and inflamed tissues grow faster. It is now becoming increasingly evident that abnormal vessel growth contributes to the pathogenesis of numerous malignant, ischaemic, inflammatory, infectious and immune disorders. With an in-depth molecular understanding, we should be better armamented to combat such angiogenic disorders in the future. That such therapeutic strategies might change the face of medicine is witnessed by initial evidence of success in the clinic.
3.
Regulation of angiogenesis by Th1- and Th2-type cytokines.
Naldini, A, Pucci, A, Bernini, C, Carraro, F
Current pharmaceutical design. 2003;(7):511-9
Abstract
Angiogenesis is a complex process, where several cell types and mediators interact to establish a specific microenvironment suitable for the formation of new capillaries from pre-existing vessels. Such biological processes occur in several physiological conditions, such as embryo development and wound healing, as well as in pathological conditions, including tumours and diabetic retinopathy. T lymphocytes, neutrophils and monocytes fully participate in the angiogenic process by secreting cytokines that may control endothelial cell (EC) proliferation, their survival and apoptosis, as well as their migration and activation. Angiogenesis is the result of a net balance between the activities exerted by positive and negative regulators. This balance is conceptually very similar to that of the Th1/Th2 cells that modulate an appropriate and specific immune response. Th1 or Th2 cytokines may control angiogenesis directly, by acting on cell growth and differentiation, indirectly by inducing the release of other cytokines in the microenvironment, and by modulating the expression of specific receptors, involved in the control of angiogenic processes, such as EC proliferation and migration. In this review we will mainly discuss the role of Th1- and Th2-type cytokines in the angiogenic process, emphasizing the complexity of the cytokine and leukocyte/EC network, and highlighting the care that needs to be taken when designing new therapeutic interventions involving Th1 and Th2 cytokines.