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Motile Cilia of Human Airway Epithel...

The University of Iowa., Molecular Physiology & Biophysics.

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Motile Cilia of Human Airway Epithelia Mediate Noncanonical Hedgehog Signaling.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Motile Cilia of Human Airway Epithelia Mediate Noncanonical Hedgehog Signaling./
作者:	Mao, Suifang.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	107 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-01, Section: B.
Contained By:	Dissertations Abstracts International80-01B.
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10237583
ISBN:	9780438151154

Motile Cilia of Human Airway Epithelia Mediate Noncanonical Hedgehog Signaling.
Mao, Suifang.

Motile Cilia of Human Airway Epithelia Mediate Noncanonical Hedgehog Signaling. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 107 p.

Source: Dissertations Abstracts International, Volume: 80-01, Section: B.

Thesis (Ph.D.)--The University of Iowa, 2018.

This item is not available from ProQuest Dissertations & Theses.

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.

ISBN: 9780438151154Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Airway epithelia

Motile Cilia of Human Airway Epithelia Mediate Noncanonical Hedgehog Signaling.
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300 $a 107 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-01, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Welsh, Michael J.
502 $a Thesis (Ph.D.)--The University of Iowa, 2018.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a 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.
590 $a School code: 0096.
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650 4 $a Physiology. $3 518431
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653 $a Motile cilia
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792 $a 2018
793 $a English
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