Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway
Abstract Substance P (SP) is a tachykinin that regulates airway mucous secretion in both health and disease. Our study aimed to determine whether overexpression of SP without pre‐existing inflammation was sufficient to induce changes in mucin secretion and transport in small airways. Utilizing porci...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-02-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.14749 |
| _version_ | 1819296248716328960 |
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| author | Mariana Sponchiado Yan‐Shin Liao Kalina R. Atanasova Emily N. Collins Veronica Schurmann Laura Bravo Leah R. Reznikov |
| author_facet | Mariana Sponchiado Yan‐Shin Liao Kalina R. Atanasova Emily N. Collins Veronica Schurmann Laura Bravo Leah R. Reznikov |
| author_sort | Mariana Sponchiado |
| collection | DOAJ |
| description | Abstract Substance P (SP) is a tachykinin that regulates airway mucous secretion in both health and disease. Our study aimed to determine whether overexpression of SP without pre‐existing inflammation was sufficient to induce changes in mucin secretion and transport in small airways. Utilizing porcine precision‐cut lung slices, we measured the impact of AAV‐mediated overexpression of SP on airway physiology ex vivo. Immunofluorescence signal intensity for MUC5AC was significantly increased in SP‐overexpressed precision‐cut lung slices compared to GFP controls. No difference in MUC5B signal intensity between treatments was detected. SP‐overexpressed precision‐cut lung slices also exhibited decreased IL10 mRNA, an important inhibitor of mucous cell metaplasia. Overt deficits in mucociliary transport were not noted, though a trend for decreased mean transport speed was detected in methacholine‐challenged airways overexpressing SP compared to GFP controls. Pharmacologic inhibition of the NF‐kβ pathway abrogated the effects of overexpression of SP on both MUC5AC and IL10. Collectively, these data suggest that overexpression of SP in the absence of existing inflammation increases MUC5AC via activation of the NF‐kβ pathway. Thus, these data further highlight SP as a key driver of abnormal mucous secretion and underscore NF‐kβ signaling as a pathway of potential therapeutic intervention. |
| first_indexed | 2024-12-24T04:55:06Z |
| format | Article |
| id | doaj.art-9d542949364441318bc0da7b9f54ed37 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-24T04:55:06Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-9d542949364441318bc0da7b9f54ed372022-12-21T17:14:25ZengWileyPhysiological Reports2051-817X2021-02-0193n/an/a10.14814/phy2.14749Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathwayMariana Sponchiado0Yan‐Shin Liao1Kalina R. Atanasova2Emily N. Collins3Veronica Schurmann4Laura Bravo5Leah R. Reznikov6Department of Physiological Sciences University of Florida Gainesville FL USADepartment of Physiological Sciences University of Florida Gainesville FL USADepartment of Physiological Sciences University of Florida Gainesville FL USADepartment of Physiological Sciences University of Florida Gainesville FL USADepartment of Physiological Sciences University of Florida Gainesville FL USADepartment of Physiological Sciences University of Florida Gainesville FL USADepartment of Physiological Sciences University of Florida Gainesville FL USAAbstract Substance P (SP) is a tachykinin that regulates airway mucous secretion in both health and disease. Our study aimed to determine whether overexpression of SP without pre‐existing inflammation was sufficient to induce changes in mucin secretion and transport in small airways. Utilizing porcine precision‐cut lung slices, we measured the impact of AAV‐mediated overexpression of SP on airway physiology ex vivo. Immunofluorescence signal intensity for MUC5AC was significantly increased in SP‐overexpressed precision‐cut lung slices compared to GFP controls. No difference in MUC5B signal intensity between treatments was detected. SP‐overexpressed precision‐cut lung slices also exhibited decreased IL10 mRNA, an important inhibitor of mucous cell metaplasia. Overt deficits in mucociliary transport were not noted, though a trend for decreased mean transport speed was detected in methacholine‐challenged airways overexpressing SP compared to GFP controls. Pharmacologic inhibition of the NF‐kβ pathway abrogated the effects of overexpression of SP on both MUC5AC and IL10. Collectively, these data suggest that overexpression of SP in the absence of existing inflammation increases MUC5AC via activation of the NF‐kβ pathway. Thus, these data further highlight SP as a key driver of abnormal mucous secretion and underscore NF‐kβ signaling as a pathway of potential therapeutic intervention.https://doi.org/10.14814/phy2.14749MUC5ACMUC5Bneuropeptidestachykinins |
| spellingShingle | Mariana Sponchiado Yan‐Shin Liao Kalina R. Atanasova Emily N. Collins Veronica Schurmann Laura Bravo Leah R. Reznikov Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway Physiological Reports MUC5AC MUC5B neuropeptides tachykinins |
| title | Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway |
| title_full | Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway |
| title_fullStr | Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway |
| title_full_unstemmed | Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway |
| title_short | Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway |
| title_sort | overexpression of substance p in pig airways increases muc5ac through an nf kβ pathway |
| topic | MUC5AC MUC5B neuropeptides tachykinins |
| url | https://doi.org/10.14814/phy2.14749 |
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