Kisspeptin调节哮喘小鼠模型的气道高反应性和重塑
2023/05/25
摘要
哮喘是一种多因素引起的疾病，以气道高反应性（AHR）和气道重塑为特征。来自其他病症的一些证据表明，Kisspeptins（Kp）调节细胞增殖、迁移和侵袭，这些机制与哮喘高度相关。我们最近的体外研究表明，Kp-10（Kp的活性肽）通过其受体KISS1R抑制人类气道平滑肌细胞的增殖。在此，我们假设Kp-10在调节体内AHR和气道重塑中起关键作用。利用C57BL/6J小鼠，我们评估了慢性鼻内Kp-10暴露对混合过敏原（MA）诱导的小鼠哮喘模型的影响。与暴露于载体（DPBS）的小鼠相比，接触MA的小鼠的肺功能明显恶化；Kp-10治疗明显改善了MA改变的肺部功能。单独用Kp-10治疗的小鼠在肺功能方面没有显示出任何明显的变化。与单独暴露于载体小鼠相比，暴露于MA的小鼠显示出KISS1R表达的明显减少。暴露于MA的小鼠在气道中的免疫细胞浸润和重塑变化方面表现出明显的改变。暴露于MA后，促炎症细胞因子明显增加，Kp-10治疗可消除这种影响。此外，生化和组织学研究显示，Kp-10暴露明显减少了MA引起的平滑肌质量和肺部可溶性胶原。总的来说，我们的发现强调了慢性Kp-10暴露在调节MA诱导的AHR和重塑方面的作用。
Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma
Borkar, N. A., Ambhore, N. S., Balraj, P., Ramakrishnan, Y. S., & Sathish, V.
ABSTRACT
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.
哮喘是一种多因素引起的疾病，以气道高反应性（AHR）和气道重塑为特征。来自其他病症的一些证据表明，Kisspeptins（Kp）调节细胞增殖、迁移和侵袭，这些机制与哮喘高度相关。我们最近的体外研究表明，Kp-10（Kp的活性肽）通过其受体KISS1R抑制人类气道平滑肌细胞的增殖。在此，我们假设Kp-10在调节体内AHR和气道重塑中起关键作用。利用C57BL/6J小鼠，我们评估了慢性鼻内Kp-10暴露对混合过敏原（MA）诱导的小鼠哮喘模型的影响。与暴露于载体（DPBS）的小鼠相比，接触MA的小鼠的肺功能明显恶化；Kp-10治疗明显改善了MA改变的肺部功能。单独用Kp-10治疗的小鼠在肺功能方面没有显示出任何明显的变化。与单独暴露于载体小鼠相比，暴露于MA的小鼠显示出KISS1R表达的明显减少。暴露于MA的小鼠在气道中的免疫细胞浸润和重塑变化方面表现出明显的改变。暴露于MA后，促炎症细胞因子明显增加，Kp-10治疗可消除这种影响。此外，生化和组织学研究显示，Kp-10暴露明显减少了MA引起的平滑肌质量和肺部可溶性胶原。总的来说，我们的发现强调了慢性Kp-10暴露在调节MA诱导的AHR和重塑方面的作用。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(J Pathol. 2023 May 12; DOI:10.1002/path.6086)
(J Pathol. 2023 May 12; DOI:10.1002/path.6086)
Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma
Borkar, N. A., Ambhore, N. S., Balraj, P., Ramakrishnan, Y. S., & Sathish, V.
ABSTRACT
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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