ABSTRACT
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.
Subject(s)
Bile Duct Diseases/pathology , Cholangitis, Sclerosing/pathology , Cicatrix/pathology , Wnt Signaling Pathway , Animals , Axin Protein/genetics , Axin Protein/metabolism , Bile Duct Diseases/chemically induced , Bile Duct Diseases/metabolism , Bile Ducts/cytology , Cell Polarity , Cholangitis, Sclerosing/metabolism , Cicatrix/metabolism , Disease Models, Animal , Epithelial Cells , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Kinase 4/metabolism , Male , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Pyridines/toxicity , Wnt Signaling Pathway/drug effects , Wnt-5a Protein/metabolismABSTRACT
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.
