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Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons™
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Full-Text Articles in Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Pharmacological Modulation Of Cgmp Levels By Phosphodiesterase 5 Inhibitors As A Therapeutic Strategy For Treatment Of Respiratory Pathology In Cystic Fibrosis., Hongwei Yu, Jens Poschet, Graham Timmons, Jennifer Taylor-Cousar, Wojciech Ornatowski, Joseph Fazio, Elizabeth Perkett, Kari Wilson, Hugo De Jonge, Vojo Deretic
Pharmacological Modulation Of Cgmp Levels By Phosphodiesterase 5 Inhibitors As A Therapeutic Strategy For Treatment Of Respiratory Pathology In Cystic Fibrosis., Hongwei Yu, Jens Poschet, Graham Timmons, Jennifer Taylor-Cousar, Wojciech Ornatowski, Joseph Fazio, Elizabeth Perkett, Kari Wilson, Hugo De Jonge, Vojo Deretic
Hongwei Yu
The CFTR gene encodes a chloride channel with pleiotropic effects on cell physiology and metabolism. Here, we show that increasing cGMP levels to inhibit epithelial Na(+) channel in cystic fibrosis (CF) respiratory epithelial cells corrects several aspects of the downstream pathology in CF. Cell culture models, using a range of CF cell lines and primary cells, showed that complementary pharmacological approaches to increasing intracellular cGMP, by elevating guanyl cyclase activity though reduced nitric oxide, addition of cell-permeable cGMP analogs, or inhibition of phosphodiesterase 5 corrected multiple aspects of the CF pathological cascade. These included correction of defective protein glycosylation, bacterial …
The Pseudomonas Aeruginosa Sensor Kinase Kinb Negatively Controls Alginate Production Through Algw-Dependent Muca Proteolysis, Hongwei Yu, F. Damron, Dongru Qiu
The Pseudomonas Aeruginosa Sensor Kinase Kinb Negatively Controls Alginate Production Through Algw-Dependent Muca Proteolysis, Hongwei Yu, F. Damron, Dongru Qiu
Hongwei Yu
Mucoidy, or overproduction of the exopolysaccharide known as alginate, in Pseudomonas aeruginosa is a poor prognosticator for lung infections in cystic fibrosis. Mutation of the anti-sigma factor MucA is a well-accepted mechanism for mucoid conversion. However, certain clinical mucoid strains of P. aeruginosa have a wild-type (wt) mucA. Here, we describe a loss-of-function mutation in kinB that causes overproduction of alginate in the wt mucA strain PAO1. KinB is the cognate histidine kinase for the transcriptional activator AlgB. Increased alginate production due to inactivation of kinB was correlated with high expression at the alginate-related promoters P(algU) and P(algD). Deletion of …