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Collagen in Atopic Dermatitis 

08/28/2024
atopic dermatitis
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Summary

In the 2024 study by Szalus et al., “The Role of Collagens in Atopic Dermatitis”, the authors highlight the importance of collagen in the extracellular matrix, which could potentially serve as a therapeutic target for atopic dermatitis.

Background 

Atopic dermatitis (AD) is a chronic, relapsing challenging inflammatory condition that presents significant challenges for both patients and providers alike. The development of AD is multifactorial, involving a complex interplay of genetic predisposition, a compromised skin barrier, and an altered microbiome. Recent research suggests a possible role for collagen in AD pathogenesis.1–3 

Pathogenesis of AD 

Collagens are essential components of the extracellular matrix (ECM), a dynamic and complex structure that regulates tissue development, cell adhesion, and intercellular communication.1–3 In the context of AD, collagens in the ECM play a crucial immunological role by influencing the migration of antigen-presenting cells such as Langerhans Cells and epidermal T lymphocytes.1,2 ECM remodeling, driven by fibroblasts, involves the production of matrix-degrading enzymes, including matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), serine proteases (e.g., plasmins), granzymes, elastases, and cathepsins.1 Notably, MMP-dependent ECM degradation induced by immune cells contributes to AD progression.1

Patients with AD exhibit elevated serum concentrations of MMP-8 and MMP-9, which perpetuate a destructive cycle of ECM remodeling and fibrosis, characteristic of the itch-scratch cycle.1 This chronic remodeling leads to overproduction of ECM components, such as Type VI collagen which has been found to be upregulated in AD compared to healthy controls.1–3 Moreover, Type VI collagen levels correlate with increased disease severity (as measured by the SCORAD index) and are lower in patients receiving calcineurin inhibitors.3 Type VI collagen, a  filamentous component forming beaded microfibrils, plays a vital role in maintaining skin homeostasis.1

Additionally, genetic studies have identified variants in the COL6A6 gene—the gene that encodes the alpha-6 chain of type VI collagen—more prevalent among AD patients, leading to decreased expression.1 Keratinocyte models have demonstrated that pro-inflammatory cytokines, including interleukin (IL)-4 and IL-13 inhibit COL6A6 expression.1 AD has also been associated with single nucleotide polymorphisms (SNPs) in other collagen-encoding genes, such as COL3A1/rs1800255 and Col6A5/29rs12488457, suggesting potential population-specific biomarkers.2 Furthermore, patients with AD also show decreased expression of type I, type III, type IV collagen, and fibronectin compared to healthy controls.1

Key Takeaway

These findings indicate that decreased COL6A6 expression, elevated IL-4 and IL-13 levels, and reduced levels of type I, III, and IV collagen compromise skin barrier integrity and weaken the basement membrane, resulting in increased skin permeability-a central feature of AD pathogenesis.1–3

Conclusion and Future Directions

Future research directions may explore the therapeutic potential of collagen tripeptide (CTP), a collagen polymer rich in the GLY-X-Y tripeptide sequence.1 Preliminary studies have shown that CTP treatment can significantly reduce inflammatory cytokine levels in keratinocytes, decrease rash area, SCORAD scores, and reduce transepidermal water loss.1 These promising findings suggest that targeting collagen-related pathways could offer new avenues for managing AD, ultimately improving patient outcomes and quality of life. 

References

1. Szalus K, Trzeciak M. The Role of Collagens in Atopic Dermatitis. Int J Mol Sci. 2024;25(14):7647. Doi:10.3390/ijms25147647

2. Szalus K, Zysk W, Gleń J, Zabłotna M, Nowicki RJ, Trzeciak M. The Associations of Single Nucleotide Polymorphisms of the COL3A1, COL6A5, and COL8A1 Genes with Atopic Dermatitis. J Pers Med. 2023;13(4):661. Doi:10.3390/jpm13040661

3. Holm Nielsen S, Port H, Møller Hausgaard C, et al. A fragment of type VI collagen alpha-6 chain is elevated in serum from patients with atopic dermatitis, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus and melanoma. Sci Rep. 2023;13(1):3056. Doi:10.1038/s41598-023-28746-2

Dr. Lio reports research grants/funding from AbbVie, AOBiome; is on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oreal, MyOR Diagnostics, ParentMD, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn, AbbVie, Almirall, Amyris, Arcutis, ASLAN, Boston Skin Science, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs, Concerto Biosci, Dermavant, Eli Lilly, Galderma, Janssen, Johnson & Johnson, Kimberly-Clark, LEO Pharma, Lipidor, L’Oreal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Skinfix, Theraplex, UCB, Unilever, Verrica Yobee Care; stock options with Codex, Concerto Biosciences and Yobee Care. In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member of the National Eczema Association.

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  • Overview

    Dr. Peter Lio and Kripa Ahuja, MS, take a closer look at a 2024 study by Szalus et al. highlighting the importance of collagen in the extracellular matrix, which could potentially serve as a therapeutic target for atopic dermatitis (AD).

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Details
Comments
  • Overview

    Dr. Peter Lio and Kripa Ahuja, MS, take a closer look at a 2024 study by Szalus et al. highlighting the importance of collagen in the extracellular matrix, which could potentially serve as a therapeutic target for atopic dermatitis (AD).

Schedule14 Oct 2024