Transcriptomic characterization of Lonrf1 at the single-cell level under pathophysiological conditions

Area of Science:

• Cellular Biology
• Molecular Biology
• Genomics

Background:

• The LONRF protein family, including LONRF1-3, possesses RING and Lon substrate binding domains.
• LONRF2 is a neuronal ubiquitin ligase crucial for protein quality control, with its absence causing neurological deficits.
• The physiological roles of other LONRF family members, particularly LONRF1, are largely unknown.

Purpose of the Study:

• To investigate the expression patterns and functional roles of Lonrf1 across different tissues and conditions.
• To analyze Lonrf1's transcriptomic impact at a single-cell level in normal and pathological states.
• To elucidate Lonrf1's potential involvement in cellular responses, tissue remodeling, and wound healing.

Main Methods:

• Single-cell expression analysis of Lonrf1.
• Transcriptomic profiling of tissues under normal and nonalcoholic steatohepatitis (NASH) conditions.
• Comparative analysis of Lonrf1 expression in fibroblasts during wound healing, considering p16 status.

Main Results:

• Lonrf1 exhibits ubiquitous expression, with increased levels in aged liver sinusoidal endothelial cells (LSECs) and Kupffer cells.
• In LSECs, Lonrf1 upregulation correlates with activated NF-kB and p53 pathways and suppressed interferon and proteasome signaling.
• Fibroblast analysis revealed distinct Lonrf1-associated signaling pathways (cell growth, TGFb/BMP, WNT) dependent on p16 expression during wound healing.

Conclusions:

• Lonrf1 is broadly expressed and dynamically regulated in various cell types, including liver cells and fibroblasts.
• Lonrf1 influences key cellular pathways involved in oxidative damage response, inflammation, and tissue remodeling.
• Lonrf1 plays a significant role in wound healing, modulating cellular behavior in both senescent and non-senescent cells, independent of senescence induction.