RESUMO
The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration.
Assuntos
Doenças dos Ductos Biliares/patologia , Colangite Esclerosante/patologia , Cicatriz/patologia , Via de Sinalização Wnt , Animais , Proteína Axina/genética , Proteína Axina/metabolismo , Doenças dos Ductos Biliares/induzido quimicamente , Doenças dos Ductos Biliares/metabolismo , Ductos Biliares/citologia , Polaridade Celular , Colangite Esclerosante/metabolismo , Cicatriz/metabolismo , Modelos Animais de Doenças , Células Epiteliais , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Piridinas/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Proteína Wnt-5a/metabolismoRESUMO
A study was conducted to find out the bacteriological quality of water during the monsoon season in local areas around Kasauli Town, and to evaluate the management of water resources in rural areas. The water samples were collected from bowries and hand pumps. As there is no municipal water supply in majority of these areas, the local residents depends mainly on these natural resources without any treatment of water. All the 14 surface water samples collected from bowries were found bacteriologically polluted with total coliform count ranging from 35-1800+. The main contaminants isolated were atypical thermotolerant E. coli, Pseudomonas fluorescence, Enterobacter cloacae, Aeromonas liquifaciens, Citrobacter freundii and Pseudomonas pseudomaleii. Among seven hand pump samples, two were found to have Coliform count 80 and 250 respectively. These two water samples were found contaminated with Citrobacter freundii and E. coli &Aeromonas liquefaciens respectively. These bacteriological contaminations appear to be both from vegetative & human or animal excreta sources. The study therefore suggested that the water from these natural resources requires treatment either by boiling or chlorination before human consumption to avoid any outbreak.
