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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Motile cilia of human airway epithelia mediate noncanonical hedgehog signaling

Mao, Suifang 01 May 2018 (has links)
During embryogenesis, airway epithelial cells possess primary cilia, and HH signaling guides lung development. As epithelial cells mature, they produce hundreds of motile cilia and continue to produce the sonic hedgehog (SHH) ligand, which is found apically in the thin layer of liquid covering airways. However, whether ciliated airway cells express apical HH signaling components and what their function might be have remained unknown. Here we show that motile cilia are enriched for HH signaling proteins, including patched 1 and smoothened. These cilia are also enriched for proteins affecting cAMP-dependent signaling, including Gαi and adenylyl cyclase 5/6. Surprisingly, SHH in differentiated airway epithelia did not elicit the canonical SHH signaling pathway that regulates transcription during development. But instead, activating HH signaling decreases intracellular levels of cAMP, which reduces ciliary beat frequency and airway surface liquid pH, similar to changes that have been observed in the airway of people with chronic obstructive pulmonary disease (COPD). Furthermore, we observed that significant increase of SHH ligand expression in differentiated airway epithelia with COPD, suggesting a potential role of SHH signaling in the pathogenesis of airway disease. Collectively, our study indicates that airway cilia detect apical SHH to mediate airway physiology through noncanonical HH signaling. SHH may dampen defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. This may suggest a potential role of SHH signaling in the pathogenesis of airway disease, such as COPD.
2

Regulation of SMC/MUC4 Expression in the Airway

Theodore, George 18 February 2010 (has links)
MUC4 is a heterodimeric mucin glycoprotein expressed in the epithelia of tissues. Previous studies in our laboratory demonstrated that MUC4 protein expression is regulated by exogenous growth factors and that MUC4 is found in complex with the receptor tyrosine kinase ErbB2. MUC4 protein expression in airway epithelia was evaluated using molecular biology techniques. The impact of the protein on ErbB2 activation was evaluated post mechanical wounding of airway epithelia, and upon MUC4 RNA silencing. MUC4 levels were increased with exposure to the differentiating agent retinoic acid and decreased upon exposure to epidermal growth factor, a proliferative agent. In the absence of MUC4, ErbB2 phosphorylation was diminished. These results support the hypothesis that MUC4 expression is enhanced during differentiation of epithelia. Furthermore these findings provide evidence for an additional level of ErbB regulation in airway injury and subsequent epithelial wound healing.
3

FXYD5 modulates Na,K-ATPase activity and is increased in cystic fibrosis airway epithelia

Miller, Timothy J. 18 April 2008 (has links)
No description available.

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