RESUMEN
An unique element of bladder urothelium is a multilayer membrane, which extends from the renal pelvis to the urethra. Urotelial membrane covers more than 90% of the inner portion of the bladder and is in direct contact with urine. Urothelium is composed of characteristic two-dimensional, asymmetric plaques, composed of uroplakins (UP), differentiated, hexagonally arranged proteins. The unique structure of the urothelial plaques determines the tightness, integrity and strength of the urothelium, prevent rupture of the walls of the bladder during the build-up of urine in the bladder and protects against the toxic ingredients. Uroplakins are tissue-specific, heterogeneous glycoproteins whose oligosaccharide part plays a specific role in the structure and function of urothelium. Disorders of normal expression of uroplakins are highly associated with the pathogenesis in infection and urinary tract malignancies, primary vesico-urinary reflux, hydronephrosis and renal impairment. The emergence of uroplakins in urine and / or plasma may have a potential role in the early detection of bladder tumors. In this paper, the structure and function of uroplakins types Ia, Ib, II, IIIa, their natural oligomerization into heterodimers, tetramers and hexamers, and the role in the construction of asymmetric and flexible urothelial epithelium is presented. We discuss the potential role of uroplakins in laboratory diagnosis of umbrella cell differentiation and in the screening analysis of urinary bladder disorders. The possibilities of using the knowledge of uroplakins in clinical settings as well as in modern strategies for treatment of infectious diseases and cancer of the urinary tract are highlighted.
Asunto(s)
Enfermedades Urológicas/diagnóstico , Enfermedades Urológicas/metabolismo , Uroplaquinas/metabolismo , Urotelio/metabolismo , Biomarcadores/metabolismo , HumanosRESUMEN
Urothelium, a specialized epithelium, covers the urinary tract and act not only as a barrier separating its light from the surrounding tissues, but fulfills an important role in maintaining the homeostasis of the urothelial tract and well-being of the whole organism. Proper function of urothelium is dependent on the precise assemble of highly specialized glycoproteins called uroplakins, the end products and differentiation markers of the urothelial cells. Glycosylation changes in uroplakins correlate with and might reflect progressive stages of pathological conditions of the urothelium such as cancer, urinary tract infections, interstitial cystitis and others. In this review we focus on sugar components of uroplakins, their emerging role in urothelial biology and disease implications. The advances in our understanding of uroplakins changes in glycan moieties composition, structure, assembly and expression of their glycovariants could potentially lead to the development of targeted therapies and discoveries of novel urine and plasma markers for the benefit of patients with urinary tract diseases.
Asunto(s)
Células Epiteliales/metabolismo , Vejiga Urinaria/metabolismo , Enfermedades Urológicas/genética , Uroplaquinas/metabolismo , Urotelio/metabolismo , Acetilglucosamina/química , Acetilglucosamina/metabolismo , Animales , Diferenciación Celular , Células Epiteliales/patología , Expresión Génica , Glicosilación , Hexosas/química , Hexosas/metabolismo , Humanos , Ácidos Siálicos/química , Ácidos Siálicos/metabolismo , Vejiga Urinaria/patología , Enfermedades Urológicas/metabolismo , Enfermedades Urológicas/patología , Uroplaquinas/química , Uroplaquinas/genética , Urotelio/patologíaRESUMEN
Human milk contains a lot of components (i.e. proteins, carbohydrates, lipids, inorganic elements) which provide basic nutrients for infants during the first period of their lives. Qualitative composition of milk components of healthy mothers is similar, but their levels change during lactation stages. Colostrum is the fluid secreted during the first days postpartum by mammary epithelial cells. Colostrum is replaced by transitional milk during 5-15 days postpartum and from 15 days postpartum mature milk is produced. Human milk, apart from nutritional components, is a source of biologically active molecules, i.e. immunoglobulins, growth factors, cytokines, acute phase proteins, antiviral and antibacterial proteins. Such components of human milk are responsible for specific biological activities of human milk. This secretion plays an important role in growth and development of newborns. Bioactive molecules present in the milk support the immature immune system of the newborn and also protect against the development of infection. In this article we describe the pathways involved in the production and secretion of human milk, the state of knowledge on the proteome of human milk, and the contents of components of milk during lactation. Moreover, some growth factors and proteins involved in innate and specific immunity, intercellular communication, immunomodulation, and inflammatory processes have been characterized.
Asunto(s)
Inmunidad Innata/inmunología , Recién Nacido/inmunología , Péptidos y Proteínas de Señalización Intercelular/inmunología , Proteínas de la Leche/inmunología , Leche Humana/inmunología , Proteínas de Fase Aguda/inmunología , Animales , Calostro/inmunología , Citocinas/inmunología , Humanos , Inmunoglobulinas/inmunología , Inmunomodulación/inmunología , Lactancia , Leche Humana/metabolismoRESUMEN
There are currently more than 80 different autoimmune diseases, affecting approximately 100 million people worldwide. The etiology of most autoimmune diseases is unknown. The highest incidence of these diseases is in the developed countries and they are more common in women than in men. Among the most often listed factors responsible for the onset of autoimmunity are genetic predisposition and the phenomenon known as molecular mimicry. The latter stems from a similarity between microbial antigens and antigens present in the human body (self antigens). It is believed that such homology is responsible for the production of auto-antibodies and in consequence attack of the immune system against host tissues and organs. However, the main molecular factors responsible for these diseases in most cases remain unknown. While pathogenesis of many autoimmune diseases indicates the presence of molecular mimicry, at the same time the similarities between the own and foreign structures do not always result in autoimmunity. Therefore, prediction of such crucial homology responsible for the development of autoimmune disease is extremely difficult. In this paper we present examples of autoimmune diseases such as type 1 diabetes, multiple sclerosis, reactive arthritis and the potential contribution of micro-organisms to the mechanism of molecular mimicry.