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Updated: Oct 21, 2025

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
Persistent JunB activation in fibroblasts disrupts stem cell niche interactions enforcing skin aging
Pallab Maity1, Karmveer Singh1, Linda Krug2
1Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany; Aging Research Center (ARC), 89081 Ulm, Germany.
Abstract:
Fibroblasts residing in the connective tissues constitute the stem cell niche, particularly in organs such as skin. Although the effect of fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. We report a mechanism of redox-dependent activation of transcription factor JunB, which, through concomitant upregulation of p16INK4A and repression of insulin growth factor-1 (IGF-1), initiates the installment of fibroblast senescence. Fibroblast senescence profoundly disrupts the metabolic and structural niche, and its essential interactions with different stem cells thus enforces depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast-niche-specific manner-by reinstatement of IGF-1 and p16 levels-restores skin stem cell pools and overall skin tissue integrity. Here, we report a role of JunB in the control of connective tissue niche and identified targets to combat skin aging and associated pathologies.
Insights
Researchers discovered that the transcription factor JunB drives fibroblast senescence, leading to skin aging. Silencing JunB rejuvenates skin stem cells and restores tissue integrity, offering targets for anti-aging therapies.
Area of Science:
- Cellular Biology
- Dermatology
- Aging Research
Background:
- Fibroblasts in connective tissue are crucial for stem cell niches, especially in skin.
- The mechanisms by which fibroblasts influence organ aging are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms of fibroblast senescence and its impact on skin aging.
- To identify JunB as a key regulator of fibroblast senescence and connective tissue niche integrity.
Main Methods:
- Investigated the role of redox-dependent activation of transcription factor JunB.
- Analyzed the upregulation of p16INK4A and repression of insulin-like growth factor-1 (IGF-1).
- Examined the effects of JunB silencing on skin stem cell pools and tissue integrity.
Main Results:
- JunB activation leads to fibroblast senescence via p16INK4A upregulation and IGF-1 repression.
- Fibroblast senescence disrupts the niche, depleting stem cell pools and causing skin decline.
- Silencing JunB restores IGF-1 and p16 levels, rejuvenating stem cells and skin tissue.
Conclusions:
- JunB is a critical regulator of the connective tissue niche and fibroblast senescence.
- Targeting JunB offers a potential therapeutic strategy for combating skin aging and related conditions.
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