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Am J Respir Cell Mol Biol ; 70(6): 507-518, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38512807

RESUMO

Airway remodeling is a cardinal feature of asthma, associated with increased airway smooth muscle (ASM) cell mass and upregulation of extracellular matrix deposition. Exaggerated ASM cell migration contributes to excessive ASM mass. Previously, we demonstrated the alleviating role of Kp (kisspeptin) receptor (KISS1R) activation by Kp-10 in mitogen (PDGF [platelet-derived growth factor])-induced human ASM cell proliferation in vitro and airway remodeling in vivo in a mouse model of asthma. Here, we examined the mechanisms by which KISS1R activation regulates mitogen-induced ASM cell migration. KISS1R activation using Kp-10 significantly inhibited PDGF-induced ASM cell migration, further confirmed using KISS1R shRNA. Furthermore, KISS1R activation modulated F/G actin dynamics and the expression of promigration proteins like CDC42 (cell division control protein 42) and cofilin. Mechanistically, we observed reduced ASM RhoA-GTPAse with KISS1R activation. The antimigratory effect of KISS1R was abolished by PKA (protein kinase A)-inhibitory peptide. Conversely, KISS1R activation significantly increased cAMP and phosphorylation of CREB (cAMP-response element binding protein) in PDGF-exposed ASM cells. Overall, these results highlight the alleviating properties of Kp-10 in the context of airway remodeling.


Assuntos
Movimento Celular , Kisspeptinas , Miócitos de Músculo Liso , Fator de Crescimento Derivado de Plaquetas , Receptores de Kisspeptina-1 , Transdução de Sinais , Proteína rhoA de Ligação ao GTP , Humanos , Movimento Celular/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Kisspeptinas/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Receptores de Kisspeptina-1/metabolismo , Receptores de Kisspeptina-1/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Remodelação das Vias Aéreas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Células Cultivadas , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Proliferação de Células
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