Kisspeptin/KISS1R Signaling Modulates Human Airway Smooth Muscle Cell Migration

被引：3

作者：

Balraj, Premanand ^{[1
]}

Ambhore, Nilesh Sudhakar ^{[1
]}

Ramakrishnan, Yogaraj S. ^{[1
]}

Borkar, Niyati A. ^{[2
]}

Banerjee, Priyanka ^{[1
]}

Reza, Mohammad Irshad ^{[1
]}

Varadharajan, Subashini ^{[1
]}

Kumar, Ashish ^{[1
]}

Pabelick, Christina M. ^{[2
,3
]}

Prakash, Y. S. ^{[2
,3
]}

Sathish, Venkatachalem ^{[1
]}

机构：

[1] North Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58102 USA

[2] Mayo Clin, Dept Anesthesiol & Perioperative Med, Rochester, MN USA

[3] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA

来源：

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | 2024年 / 70卷 / 06期

基金：

美国国家卫生研究院;

关键词：

airway remodeling; mitogen; asthma; actin dynamics; cAMP-dependent protein kinase A; PROTEIN-COUPLED RECEPTOR; KISS-1; EXPRESSION; PATHWAY; CREB; PKA; PROLIFERATION; INHIBITION; SUPPRESSES; INVASION;

D O I：

10.1165/rcmb.2023-0469OC

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Airway remodeling is a cardinal feature of asthma, associated with increased airway smoothmuscle (ASM) cellmass andupregulationof extracellularmatrix deposition. Exaggerated ASMcellmigration contributes to excessive ASMmass. Previously, we demonstrated the alleviating role of Kp (kisspeptin) receptor (KISS1R) activation by Kp-10 inmitogen (PDGF [platelet-derived growth factor])-induced human ASMcell proliferation in vitro and airway remodeling in vivo in amousemodel of asthma. Here, we examined themechanisms by which KISS1R activation regulatesmitogen-induced ASM cell migration. KISS1R activation using Kp-10 significantly inhibited PDGF-induced ASMcellmigration, further confirmed using KISS1R shRNA. Furthermore, KISS1R activationmodulated 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 ASMcells. Overall, these results highlight the alleviating properties of Kp-10 in the context of airway remodeling.

引用

页码：507 / 518

页数：12