Kisspeptin/KISS1R Signaling Modulates Human Airway Smooth Muscle Cell Migration.
Premanand Balraj, Nilesh Sudhakar Ambhore, Yogaraj S Ramakrishnan, Niyati A Borkar, Priyanka Banerjee, Mohammad Irshad Reza, Subashini Varadharajan, Ashish Kumar, Christina M Pabelick, Y S Prakash, Venkatachalem Sathish
Author Information
Premanand Balraj: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Nilesh Sudhakar Ambhore: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Yogaraj S Ramakrishnan: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Niyati A Borkar: Department of Anesthesiology and Perioperative Medicine, and. ORCID
Priyanka Banerjee: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Mohammad Irshad Reza: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Subashini Varadharajan: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Ashish Kumar: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
Christina M Pabelick: Department of Anesthesiology and Perioperative Medicine, and. ORCID
Y S Prakash: Department of Anesthesiology and Perioperative Medicine, and. ORCID
Venkatachalem Sathish: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota. ORCID
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 and airway remodeling 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.
