Biology subjects

Rebane, A.

Publications and source records attributed to Rebane, A..

3 recordsLinked to original sources

bioRxiv2026

MicroRNA-378a-3p Modulates Inflammatory Responses of Keratinocytes to Atopic Dermatitis-Related Cytokines or Staphylococcus aureus

miR-378a-3p has been reported to be upregulated in the lesional skin of patients with atopic dermatitis (AD); however, its function in AD remains unclear. Here, we demonstrate that miR-378a-3p expression is induced by IL-4 and live Staphylococcus aureus (S. aureus) in normal human epidermal keratinocytes (NHEKs) cultured in proliferative conditions or in a 3D epidermal culture model. Transcriptomic profiling and gene set enrichment analysis of miR-378a-3p-transfected NHEKs revealed positive enrichment of inflammatory response pathways alongside downregulation of genes associated with epidermal development. More specifically, miR-378a-3p enhanced expression of multiple NF-{kappa}B-dependent inflammatory mediators, accompanied by increased phosphorylation of p65, indicating activation of canonical NF-{kappa}B pathway. Notably, miR-378a-3p concomitantly reduced the expression of several NF-{kappa}B family members and upstream adaptor molecules, supporting a model in which miR-378a-3p promotes canonical NF-{kappa}B activity through coordinated modulation of multiple components within the NF-{kappa}B regulatory network. In NHEKs exposed to live S. aureus, miR-378a-3p significantly increased the secretion of IL-1{beta}, IL-1Ra, and IL-8, indicating that miR-378a-3p may amplify innate immune responses triggered by S. aureus colonization in AD. Collectively, these findings identify miR-378a-3p as a positive regulator of keratinocyte inflammatory responses that may contribute to AD exacerbation, particularly in the context of S. aureus colonization.

immunology↗

bioRxiv2023

Phase-Separated Droplets Swim to Their Dissolution

Biological macromolecules can condense into liquid domains. In cells, these condensates form membraneless organelles that can organize chemical reactions1,2. However, little is known about the physical consequences of chemical activity in and around condensates. Working with model bovine serum albumin (BSA) condensates3, we show that droplets swim along chemical gradients. Active BSA droplets loaded with urease swim toward each other. Passive BSA droplets show diverse responses to externally applied gradients of the enzymes substrate and products. In all these cases, droplets swim toward solvent conditions that favor their dissolution. We call this behavior dialytaxis, and expect it to be generic, as conditions which favor dissolution typically reduce interfacial tension, whose gradients are well-known to drive droplet motion4,5. These results suggest alternative physical mechanisms for active transport in living cells, and may enable the design of fluid micro-robots.

biophysics↗

bioRxiv2021

Divalent metal ions boost effect of nucleic acids delivered by cell-penetrating peptides

Cell-penetrating peptides (CPPs) are promising tools for transfection of various substances, including nucleic acids, into cells. The aim of current work was to search for novel safe and effective approaches for enhancing transfection efficiency of nanoparticles formed of CPP and splice-correcting oligonucleotide (SCO) without increasing the concentration of peptide. We analyzed an effect of inclusion of calcium and magnesium ions into nanoparticles on CPP-mediated transfection in cell culture. We also studied the mechanism of such transfection as well as its efficiency, applicability in case of different cell lines, nucleic acid types and peptides, and possible limitations. We discovered a strong positive effect of these ions on transfection efficiency of SCO, that translated to enhanced synthesis of functional reporter protein. We observed significant changes in intracellular distribution and trafficking of nanoparticles formed with addition of the ions, without increasing cytotoxicity. We propose a novel strategy of preparing CPP-oligonucleotide nanoparticles with enhanced efficiency and, thus, higher therapeutic potential. Our discovery may be translated to primary cell cultures and, possibly, in vivo studies, in the aim to increase CPP-mediated transfection efficiency and likelihood of using CPPs in clinics.

cell biology↗