Surface Lin28A expression consistent with cellular stress parallels indicators of senescence

Area of Science:

• Cardiovascular Biology
• Cellular Stress Response
• Aging Research

Background:

• Myocardial performance declines with cellular stress and aging.
• Cardiac interstitial cells (CICs) are key in stress and aging responses.
• The role of RNA-binding protein Lin28A in CIC stress response is unexplored.

Purpose of the Study:

• Investigate the role of Lin28A in CICs under stress.
• Determine if surface Lin28A is a marker for stress in CICs.
• Explore Lin28A's connection to aging and senescence in CICs.

Main Methods:

• Assessed Lin28A localization in murine CICs.
• Correlated Lin28A with oxidative stress, senescence, and ploidy.
• Utilized single-cell RNA-Seq for transcriptional profiling.

Main Results:

• Surface Lin28A increased in CICs under hyperoxic stress.
• Surface Lin28A correlated with senescence markers (p16, β-gal) and polyploidization.
• Oxidative stress pathways were upregulated in CICs with surface Lin28A.
• Antioxidant Trolox blunted Lin28A induction in a dose-dependent manner.

Conclusions:

• Surface Lin28A serves as a marker for oxidative stress in CICs.
• Antioxidant treatment can counteract the stress-induced Lin28A phenotype.
• Lin28A surface expression offers insights into mitigating cardiac stress and aging.