Molecular determinants of airway smooth muscle cells in health and disease

Ambhore, Nilesh Sudhakar; Kumar, Ashish; Sathish, Venkatachalem

doi:10.21037/atm-22-4478

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Effect of Kp-10 on α-smooth muscle actin (α-SMA) and vimentin in the lung α-SMA is often considered a characteristic marker for smooth muscle and was found to be increased during airway remodeling [38]. Vimentin is an intermediate filament protein involved in phenotype changes during lung fibrosis [26,28].…”

Section: Effect Of Kp-10 On Airway Structure and Morphologymentioning

confidence: 99%

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Borkar

Ambhore

Balraj

et al. 2023

The Journal of Pathology

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Asthma is a multifactorial disease of origin characterized by airway hyperresponsiveness (AHR) and airway remodeling. Several pieces of evidence from other pathologies suggest that Kisspeptins (Kp) regulate cell proliferation, migration, and invasion, mechanisms that are highly relevant to asthma. Our recent in vitro studies show Kp‐10 (active peptide of Kp), via its receptor, KISS1R, inhibits human airway smooth muscle cell proliferation. Here, we hypothesize a crucial role for Kp‐10 in regulating AHR and airway remodeling in vivo. Utilizing C57BL/6J mice, we assessed the effect of chronic intranasal Kp‐10 exposure on mixed allergen (MA)‐induced mouse model of asthma. MA‐challenged mice showed significant deterioration of lung function compared to those exposed to vehicle (DPBS); Kp‐10 treatment significantly improved the MA‐altered lung functions. Mice treated with Kp‐10 alone did not show any notable changes in lung functions. MA‐exposed mice showed a significant reduction in KISS1R expression as compared to vehicle alone. MA‐challenged mice showed significant alterations in immune cell infiltration in the airways and remodeling changes. Proinflammatory cytokines were significantly increased upon MA exposure, an effect abrogated by Kp‐10 treatment. Furthermore, biochemical and histological studies showed Kp‐10 exposure significantly reduced MA‐induced smooth muscle mass and soluble collagen in the lung. Overall, our findings highlight the effect of chronic Kp‐10 exposure in regulating MA‐induced AHR and remodeling. © 2023 The Pathological Society of Great Britain and Ireland.

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Section: Effect Of Kp-10 On Airway Structure and Morphologymentioning

confidence: 99%

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Borkar

Ambhore

Balraj

et al. 2023

The Journal of Pathology

Self Cite

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Estrogen receptors differentially modifies lamellipodial and focal adhesion dynamics in airway smooth muscle cell migration

Ambhore,

Balraj,

Pabelick

et al. 2024

Molecular and Cellular Endocrinology

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Kiss1 receptor knockout exacerbates airway hyperresponsiveness and remodeling in a mouse model of allergic asthma

Ambhore,

Balraj,

Kumar

et al. 2024

Respir Res

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Background In asthma, sex-steroids signaling is recognized as a critical regulator of disease pathophysiology. However, the paradoxical role of sex-steroids, especially estrogen, suggests that an upstream mechanism or even independent of estrogen plays an important role in regulating asthma pathophysiology. In this context, in our previous studies, we explored kisspeptin (Kp) and its receptor Kiss1R’s signaling in regulating human airway smooth muscle cell remodeling in vitro and airway hyperresponsiveness (AHR) in vivo in a mouse (wild-type, WT) model of asthma. In this study, we evaluated the effect of endogenous Kp in regulating AHR and remodeling using Kiss1R knockout (Kiss1R −/− ) mice. Methods C57BL/6J WT (Kiss1R +/+ ) and Kiss1R −/− mice, both male and female, were intranasally challenged with mixed-allergen (MA) and/or phosphate-buffered saline (PBS). We used flexiVent analysis to assess airway resistance (Rrs), elastance (Ers), and compliance (Crs). Following this, broncho-alveolar lavage (BAL) was performed for differential leukocyte count (DLC) and cytokine analysis. Histology staining was performed using hematoxylin and eosin (H&E) for morphological analysis and Masson’s Trichrome (MT) for collagen deposition. Additionally, lung sections were processed for immunofluorescence (IF) of Ki-67, α-smooth muscle actin (α-SMA), and tenascin-c. Results Interestingly, the loss of Kiss1R exacerbated lung function and airway contractility in mice challenged with MA, with more profound effects in Kiss1R −/− female mice. MA-challenged Kiss1R −/− mice showed a significant increase in immune cell infiltration and proinflammatory cytokine levels. Importantly, the loss of Kiss1R aggravated Th2/Th17 biased cytokines in MA-challenged mice. Furthermore, histology of lung sections from Kiss1R −/− mice showed increased collagen deposition on airway walls and mucin production in airway cells compared to Kiss1R +/+ mice. In addition, immunofluorescence analysis showed loss of Kiss1R significantly aggravated airway remodeling and subsequently AHR. Conclusions These findings demonstrate the importance of inherent Kiss1R signaling in regulating airway inflammation, AHR, and remodeling in the pathophysiology of asthma. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-024-03017-4.

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Molecular determinants of airway smooth muscle cells in health and disease

Cited by 3 publications

References 24 publications

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Estrogen receptors differentially modifies lamellipodial and focal adhesion dynamics in airway smooth muscle cell migration

Kiss1 receptor knockout exacerbates airway hyperresponsiveness and remodeling in a mouse model of allergic asthma

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