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Nd:YAG Laser Treats Rosacea Caused by the Antimicrobial Peptide LL-37 by Remodeling Skin Collagen in Mice

evidence
The takeaway

A long-pulsed Nd:YAG laser reduced rosacea-like skin lesions induced by the cathelicidin peptide LL-37 in mice by promoting collagen remodeling through increased TGF-β and MMP-1 expression.

Collagen, TGF-β, and MMP-1 all significantly increased

Laser treatment activated a three-part collagen remodeling cascade in rosacea-affected skin — increased growth factor, increased collagen-breaking enzyme, and increased new collagen production — suggesting the laser works by rebuilding damaged skin from within.

What the researchers found

Long-pulsed 1064-nm Nd:YAG laser treatment significantly reduced erythema (redness) and increased dermal collagen production in LL-37-induced rosacea-like skin lesions. Laser-treated mice showed significantly higher mRNA levels of type I collagen, TGF-β (a growth factor that promotes tissue repair), and MMP-1 (an enzyme that breaks down damaged collagen) compared to untreated mice.

These results suggest the laser works by triggering MMP-mediated collagen remodeling — essentially clearing out disorganized connective tissue and replacing it with healthy new collagen, which addresses the dermal damage underlying rosacea rather than just treating surface symptoms.

Why it matters

This study provides molecular evidence for why Nd:YAG laser therapy works for rosacea, a condition affecting an estimated 5% of the global population. By showing that the laser promotes collagen remodeling rather than just reducing surface redness, it supports the use of laser treatment to address deeper structural skin damage in rosacea. It also reinforces the central role of LL-37 in rosacea pathology.

How the study worked

Researchers injected the cathelicidin peptide LL-37 intradermally into the dorsal skin of 30 BALB/c mice twice daily for 2 days to induce rosacea-like lesions. Fifteen mice were then treated with long-pulsed Nd:YAG laser. After 48 hours, skin samples were excised and analyzed using histology, collagen staining, and real-time RT-PCR to measure mRNA levels of type I collagen, TGF-β, MMP-1, TIMP-1, TNF-α, and IL-1α.

What this study cannot tell us

This was a mouse study using an artificial rosacea model (intradermal LL-37 injection), which may not fully replicate the chronic, multifactorial nature of human rosacea. The sample size was small (30 mice total), the observation period was short (48 hours post-treatment), and the study measured mRNA expression rather than long-term clinical outcomes. Mouse skin differs structurally from human facial skin.

How to read the evidence

This is a preclinical animal study using a controlled mouse model of rosacea. While the experimental design with treatment and control groups is sound, the artificial nature of the LL-37 injection model and the differences between mouse and human skin limit direct clinical applicability.

When this study was published

Published in 2018, this study is several years old but remains relevant as Nd:YAG laser therapy continues to be widely used for rosacea and LL-37 remains a central focus of rosacea research.

The bigger picture

The cathelicidin peptide LL-37 has emerged as a key driver of rosacea inflammation over the past two decades. This study connects two important lines of research: the peptide-driven pathology of rosacea and the clinical effectiveness of laser treatment. By demonstrating that laser therapy counteracts LL-37's skin damage through collagen remodeling, it opens the door to combination approaches that might target both the peptide trigger and the structural damage simultaneously.

Questions still open

  • Would combining Nd:YAG laser treatment with therapies that reduce LL-37 production (such as topical antibiotics) produce better rosacea outcomes than either alone?
  • Do the collagen remodeling effects persist long-term, or is repeated laser treatment needed to maintain results?
  • Could measuring LL-37 levels in patient skin help predict which rosacea patients would respond best to laser therapy?

Common questions

What is LL-37 and what does it have to do with rosacea?
LL-37 is a cathelicidin antimicrobial peptide — a natural immune defense molecule produced by skin cells. In people with rosacea, LL-37 is overproduced and abnormally processed, triggering excessive inflammation, blood vessel dilation, and redness. Injecting LL-37 into mouse skin is a well-established method for creating rosacea-like lesions in research.
How does Nd:YAG laser treatment help with rosacea?
According to this study, the laser works by promoting collagen remodeling in the deeper layers of the skin. It activates enzymes (MMP-1) that break down the disorganized, damaged collagen caused by rosacea inflammation, while simultaneously stimulating growth factors (TGF-β) that promote the production of healthy new collagen. This addresses the structural skin damage underlying rosacea, not just the surface redness.

Read the original research

Long-pulsed 1064-nm Nd: YAG laser ameliorates LL-37-induced rosacea-like skin lesions through promoting collagen remodeling in BALB/c mice.

Lasers in medical science, 33(2), 393-397

Citation

Kim, Miri; Kim, Jongsic; Jeong, Seo-Won; Jo, Hyunmu; Park, Hyun Jeong. (2018). Long-pulsed 1064-nm Nd: YAG laser ameliorates LL-37-induced rosacea-like skin lesions through promoting collagen remodeling in BALB/c mice.. Lasers in medical science, 33(2), 393-397. https://doi.org/10.1007/s10103-017-2410-8