Journal de génomique clinique et médicale

NRP1 Activates NF-κB Signaling Pathway and Initiates Proliferation in Keratinocytes

Abstract

Nikoletta Nagy, Katalin Farkas, Sarolta Bacsa, Istvan Balazs Nemeth, Zsuzsanna Bata-Csorgo, Lajos Kemeny and Marta Szell

Background: Neuropilin-1 (NRP1) is a membrane-bound co-receptor of vascular endothelial growth factor receptors (VEGFRs) and type-A plexins. These complexes mediate the effects of ligands such as vascular endothelial growth factor 165 (VEGF₁₆₅) and semaphorin 3A (SEMA-3A).

Aim: Our aims were to elucidate whether the expression of NRP1 is related to the proliferation or differentiation programme of keratinocytes and to identify putative downstream signaling pathways of NRP1 in keratinocytes.

Materials and methods: Synchronized HaCaT cells and paraffin-embedded tissue samples of psoriasis were used to modell highly proliferative stages of keratinocytes. Real-time RT-PCR-based expression array was used to analyse downstream signaling pathways in keratinocytes.

Results: Synchronized HaCaT cells revealed that the peak expression of NRP1 occurred 24 hours before the cells reached their highest proliferative activity. Immunohistochemical staining of the highly proliferative tissue samples demonstrated that the high level of NRP1 protein expression partially overlapped with the expression of Ki67-positive cells. Real-time RT-PCR-based expression array identified the NF-κB pathway as one putative downstream signaling pathway of NRP1-mediated signaling in HaCaT cells. VEGF₁₆₅ and SEMA-3A treatment of HaCaT cells stably transformed with a reporter construct for the assessment of NF-κB activation led to upregulation of the NF-κB activity.

Conclusion: Our results suggest that the NRP1 might be involved in the regulation of keratinocyte proliferation and might activate NF-κB pathway as a putative downstream signaling pathway in keratinocytes.