Biology subjects

Korfei, M.

Publications and source records attributed to Korfei, M..

3 recordsLinked to original sources

bioRxiv2026

Aging reprograms the response to chronic stress

Chronic stress is thought to accelerate brain aging. We find this to be true in the brains of young mice, but reversed in the old. Using chronic variable stress in young (2-month) and aged (24-month) mice, we show that aged animals perceive stress physiologically but exhibit stress-responses that differ from those of young mice on behavioral, synaptic, and molecular levels. Multi-Omics profiling of prefrontal cortex and nucleus accumbens and 3D vasculature measurements reveals that stress in aged mice activates angiogenic programs that oppose aging-related patterns. Our results demonstrate that stress cannot be universally conceptualized as an aging accelerator, but instead engages age-specific programs with opposite directionality in young and old animals.

neuroscience↗

bioRxiv2021

Identification of Paired-related Homeobox Protein 1 as a key mesenchymal transcription factor in Idiopathic Pulmonary Fibrosis

Matrix remodeling is a salient feature of idiopathic pulmonary fibrosis (IPF). Targeting cells driving matrix remodeling could be a promising avenue for IPF treatment. Analysis of transcriptomic database identified the mesenchymal transcription factor PRRX1 as upregulated in IPF. PRRX1, strongly expressed by lung fibroblasts, was regulated by a TGF-{beta}/PGE2 balance in vitro in control and IPF fibroblasts, while IPF fibroblast-derived matrix increased PRRX1 expression in a PDGFR dependent manner in control ones. PRRX1 inhibition decreased fibroblast proliferation by downregulating the expression of S phase cyclins. PRRX1 inhibition also impacted TGF-{beta} driven myofibroblastic differentiation by inhibiting SMAD2/3 phosphorylation through phosphatase PPM1A upregulation and TGFBR2 downregulation, leading to TGF-{beta} response global decrease. Finally, targeted inhibition of Prrx1 attenuated fibrotic remodeling in vivo with intra-tracheal antisense oligonucleotides in bleomycin mouse model of lung fibrosis and ex vivo using precision-cut lung slices. Our results identified PRRX1 as a mesenchymal transcription factor driving lung fibrogenesis. Brief SummaryInhibition of a single fibroblast-associated transcription factor, namely paired-related homeobox protein 1, is sufficient to dampen lung fibrogenesis.

cell biology↗

bioRxiv2019

Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition

Alveolar epithelial cell type II (AEC2) injury underlies idiopathic pulmonary fibrosis (IPF). Here we show increased Notch1 signaling in AEC2s in human IPF and IPF models, causing enhanced proliferation and de-differentiation of AEC2s. As a result, we observed defective surfactant protein (SP)-B/C processing, elevated alveolar surface tension, repetitive alveolar collapse and development of lung fibrosis. Similar changes were encountered upon pharmacological inhibition of SP-B/C processing in vivo by pepstatin A. Inhibition of Notch signaling in cultured human IPF precision cut lung slices improved surfactant processing capacity of AEC2s and reversed fibrosis. Notch1 therefore offers as novel therapeutic target.\n\nOne sentence summaryNotch1 inhibition restores alveolar epithelial differentiation and surface tension and reverses matrix deposition in lung fibrosis

cell biology↗