PDGF promotes the interaction of nesprin-1 with NUP62 in human airway smooth muscle cells

Asthma is characterized by airway remodeling, which is attributed to airway smooth muscle proliferation. The mechanisms that orchestrate smooth muscle proliferation are not entirely understood. Nesprin-1 (also called SYNE-1) resides on nuclear envelop and connects actin filaments with the nucleoskeleton. We have previously found that expression of nesprin-1 was upregulated in asthmatic human airway smooth muscle (HASM) cells. Nesprin-1 knockdown (KD) inhibited STAT3 nuclear import and cell proliferation in response to stimulation with platelet-derived growth factor (PDGF). Here, PDGF stimulation elicited the association of nesprin-1 with NUP 62 (a component of nuclear pore complex) as evidenced by immunofluorescence microscopy. PDGF stimulation also induced acetylation of NUP62 at K22, which was mediated by p300 acetyltransferase. Moreover, nesprin-1 KD diminished NUP62 acetylation at K22. These studies suggest that PDGF stimulation enhances the interaction of nesprin-1 with NUP62, which facilitates NUP62 acetylation, STAT3 nuclear import and cell proliferation.