For decades, scientists believed that dermal fibroblasts were solely responsible for producing type I collagen—the major structural protein in our skin. However, new research on axolotl skin has overturned this long-standing belief, revealing that keratinocytes, the cells that make up the outer layer of the skin, also contribute significantly to collagen formation. This breakthrough could have major implications for regenerative medicine, dermatology, and anti-aging treatments.

A team of researchers led by Ayaka Ohashi and colleagues at Okayama University used the transparent skin of axolotls—salamanders renowned for their regenerative abilities—to track collagen formation in real-time. By using fluorescent markers, they observed that keratinocytes, rather than fibroblasts, were the primary source of collagen in early skin development. Fibroblasts still played an important role, but rather than creating collagen from scratch, they modified and reinforced the collagen network initially laid down by keratinocytes.

This discovery has far-reaching implications. First, it challenges the fundamental understanding of skin biology. If keratinocytes play a role in collagen production, this could explain why certain skin treatments, like retinoids and chemical peels, stimulate collagen synthesis. It also raises the possibility that we could enhance collagen production in aging skin by targeting keratinocytes, rather than just fibroblasts.

Moreover, the researchers found that this keratinocyte-driven collagen production is not unique to axolotls. They confirmed similar mechanisms in zebrafish, chickens, and even mouse embryos, suggesting it is an evolutionary feature shared across multiple species. This means that insights from the axolotl model could be directly applicable to human skin biology.

The findings pave the way for new skincare and medical treatments. If scientists can harness the ability of keratinocytes to produce collagen, it may be possible to develop novel therapies to prevent wrinkles, improve wound healing, and even treat skin diseases that involve collagen defects.

This research not only changes our understanding of how skin is built but also opens exciting new doors for improving human skin health.

Source:
https://www.nature.com/articles/s41467-025-57055-7#:~:text=It%20is%20also%20possible%20that,dermis%20through%20the%20basement%20membrane.
Ohashi, A., Sakamoto, H., Kuroda, J., Kondo, Y., Kamei, Y., Nonaka, S., Furukawa, S., Yamamoto, S., & Satoh, A. (2025). Keratinocyte-driven dermal collagen formation in the axolotl skin. Nature Communications, 16, Article 1757.