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Integrin-Binding Matricellular Protein Fibulin-5 Maintains Epidermal Stem Cell Heterogeneity During Skin Aging
Wenxin Fan1,2,3, Mizuho Ishikawa1,2, Erna Raja1,4
1International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.
Aging Cell
|April 10, 2026
Summary
Fibulin-5 (Fbln5) loss impairs epidermal stem cell function during skin aging. This extracellular matrix protein maintains stem cell balance by influencing YAP signaling and cell density responses.
Area of Science:
- Dermatology
- Cell Biology
- Aging Research
Background:
- The extracellular matrix (ECM) is vital for tissue function and cellular signaling.
- Fibulin-5 (Fbln5), an ECM protein, is crucial for elastic fibers and cell regulation.
- Fbln5 declines with age in human skin, but its role in epidermal stem cells is unclear.
Purpose of the Study:
- To investigate the role of Fibulin-5 (Fbln5) in epidermal stem cell regulation during skin aging.
- To explore the molecular mechanisms linking Fbln5 to stem cell function and YAP signaling.
Main Methods:
- Mice lacking Fbln5 were analyzed for epidermal stem cell properties.
- Integrin and cell junction protein expression was assessed.
- YAP activation, cell density effects, and SLC1A3 expression were studied in vitro and in vivo.
Main Results:
- Fbln5 deficiency in mice caused early epidermal stem cell defects mimicking aged skin.
- Reduced integrin and cell junction proteins, along with decreased YAP activation, were observed in Fbln5-deficient stem cells.
- Cell density modulated YAP activity and SLC1A3 expression, with Fbln5 coating partially restoring these under high density.
Conclusions:
- Fibulin-5 (Fbln5) is essential for maintaining epidermal stem cell balance during skin aging.
- Fbln5 influences stem cell function by linking extracellular changes to intracellular YAP signaling.
- These findings highlight Fbln5's non-structural role in regulating stem cell homeostasis via the ECM-YAP axis.
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