Plastic associated endocrine disruptors reduce Nicastrin protein and potentiate inflammation in hidradenitis suppurativa skin disease

Kaitlin L. Williams, Beita Badiei, James Reilly, William Andrews, Hana B. Minsky, Nina Rossa Haddad, Eddie G. Martinez Pena, Mengqi Sun, Sam Lee, Ang Li, Leigh Curvin-Aquilla, Arieana Y. Johnson, Aiden Willis, Charles S. Kirby, Amy van Ee, Yingchao Xue, Carrie A. Cox, Shanmuga Priya Rajagopalan, Sewon Kang, Kurunthachalam Kannan, Julie Caffrey, Nathan K. Archer, Maureen Kane and Luis A. Garza ()
Additional contact information
Kaitlin L. Williams: Johns Hopkins University School of Medicine, Department of Dermatology
Beita Badiei: Johns Hopkins University School of Medicine, Department of Dermatology
James Reilly: Johns Hopkins University School of Medicine, Department of Dermatology
William Andrews: University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences
Hana B. Minsky: Johns Hopkins University School of Medicine, Department of Dermatology
Nina Rossa Haddad: Johns Hopkins University School of Medicine, Department of Dermatology
Eddie G. Martinez Pena: Johns Hopkins University School of Medicine, Department of Dermatology
Mengqi Sun: Johns Hopkins University School of Medicine, Department of Dermatology
Sam Lee: Johns Hopkins University School of Medicine, Department of Dermatology
Ang Li: Johns Hopkins University School of Medicine, Department of Dermatology
Leigh Curvin-Aquilla: Johns Hopkins University School of Medicine, Department of Dermatology
Arieana Y. Johnson: Johns Hopkins University School of Medicine, Department of Dermatology
Aiden Willis: Johns Hopkins University School of Medicine, Department of Dermatology
Charles S. Kirby: Johns Hopkins University School of Medicine, Department of Dermatology
Amy van Ee: Johns Hopkins University School of Medicine, Department of Dermatology
Yingchao Xue: Johns Hopkins University School of Medicine, Department of Dermatology
Carrie A. Cox: Johns Hopkins University School of Medicine, Department of Plastic and Reconstructive surgery
Shanmuga Priya Rajagopalan: Johns Hopkins University School of Medicine, Department of Plastic and Reconstructive surgery
Sewon Kang: Johns Hopkins University School of Medicine, Department of Dermatology
Kurunthachalam Kannan: New York State Department of Health, Wadsworth Center
Julie Caffrey: Johns Hopkins University School of Medicine, Department of Plastic and Reconstructive surgery
Nathan K. Archer: Johns Hopkins University School of Medicine, Department of Dermatology
Maureen Kane: University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences
Luis A. Garza: Johns Hopkins University School of Medicine, Department of Dermatology

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Hidradenitis Suppurativa (HS) is an inflammatory skin disorder with limited treatments and unclear etiology. While monogenic HS is linked to gamma secretase mutations, particularly in the NCSTN subunit, the pathogenesis of the more common sporadic form remains uncertain, though associated with risk factors such as diets high in ultra-processed foods. Consistent with the clinical overlap between sporadic and monogenic HS, we find loss of NCSTN protein in sporadic HS fibroblasts. We hypothesize the rising incidence of sporadic HS and its hormonal associations implicate endocrine-disrupting chemicals, especially plastic-associated EDCs (p-EDs) common in UPFs. We detect elevated p-ED adducts in HS skin, persisting in ex vivo cultured fibroblasts. At nanomolar concentrations, p-EDs inhibits NCSTN and primes fibroblasts for inflammation, mimicking NCSTN knockdown. These findings suggest p-ED exposure contributes to HS pathogenesis, highlighting the need to address environmental exposures in HS and other gamma secretase-related diseases.

Date: 2025
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DOI: 10.1038/s41467-025-65789-7

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