Biology subjects

Ferrarese, L.

Publications and source records attributed to Ferrarese, L..

2 recordsLinked to original sources

bioRxiv2026

An FGF7-FGFR2-KLF4 feedback loop sustains anti-inflammatory signaling in epithelial cells

Chronic or excessive inflammation are hallmarks of many human diseases, but the endogenous factors that limit inflammatory responses are insufficiently characterized. We discovered a broad anti-inflammatory function of fibroblast growth factor 7 (FGF7), which is mediated via epithelial cels. FGF7 suppressed the expression of pro-inflammatory and immunomodulatory genes in cultured human keratinocytes in the absence or presence of pro-inflammatory stimuli and in a psoriasiform inflammation model in mice. Mechanistically, this involves an FGF7-FGF receptor 2 (FGFR2)-MAPK-Kruppel-like factor 4 (KLF4) signaling axis. FGF7 induced significant alterations in the KLF4 interactome in human keratinocytes and suppressed the transcriptional activity of KLF4 at its pro-inflammatory target genes. Concomitantly, expression of FGFR2 and downstream signaling components was promoted by KLF4, identifying a KLF4-dependent regulatory feedback loop that sustains anti-inflammatory FGF signaling. These results suggest activation of FGF7-FGFR2-KLF4 signaling as a strategy for the treatment of inflammatory diseases involving the skin or other epithelial tissues and highlight the role of epithelial cells in the control of inflammation.

cell biology↗

bioRxiv2023

Atypical cortical feedback underlies failure to process contextual information in the superior colliculus of Scn2a+/- autism model mice

Atypical sensory integration and contextual learning are common symptoms in autism spectrum disorder (ASD), but how sensory circuits are affected remains elusive. Here we focused on the early visual information processing, and performed in vivo two-photon calcium imaging and pupillometry of mice engaged in an implicit learning task in stable and volatile visual contexts. Wild-type (WT) mice showed stimulus-specific contextual modulation of the visual responses in the superior colliculus (SC) and pupil dynamics, whereas Scn2a-haploinsufficient ASD-model mice exhibited abnormal modulation patterns. In both genotypes, feedforward inputs from the retina to SC demonstrated no such contextual modulation. In contrast, feedback inputs from the primary visual cortex (V1) showed modulation patterns similar to those of SC cells in WT mice, but no modulation in Scn2a+/- mice. Furthermore, chemogenetic perturbation revealed that this top-down signaling from V1 to SC mediated the observed contextual modulation both at the neurophysiological and behavioral levels. These results suggest that the corticotectal input is critical for contextual sensory integration in SC, and its anomaly underlies atypical sensory learning in ASD.

neuroscience↗