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The following is a summary of “Targeting the Galectin-7/TRPM2/Zn2+/DRP-1 Signaling Pathway: A Potential Therapeutic Intervention in the Pathogenesis of SJS/TEN,” published in the March 2025 issue of European Journal of Allergy and Clinical Immunology by Zhang et al. 

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced skin reactions marked by widespread keratinocyte apoptosis which differentiates them from erythema multiforme (EM). 

Researchers conducted a retrospective study on the role of mitochondrial-dependent apoptosis in SJS/TEN.  

They conducted proteomic analyses on blister fluid (BF)-derived exosomes from healthy individuals (Con Exo) or patients with EM (EM Exo), and SJS/TEN (TEN Exo). They used GST pull-down assay, liquid chromatography–tandem mass spectrometry (LC–MS/MS), proximity ligation assay (PLA), and coimmunoprecipitation (co-IP) for validation. Phenotypic and mechanistic analyses included immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), western blotting, reverse transcription–polymerase chain reaction (RT-PCR), co-IP, CCK-8 assay, adenosine triphosphate (ATP) measurements, and flow cytometry. 

The results showed galectin-7 was highly upregulated in BF-derived exosomes from SJS/TEN patients, correlating with disease severity. Galectin-7 interacted with TRPM2, leading to imbalance in mitochondrial dynamics. Transient receptor potential (melastatin) 2 (TRPM2) activation increased mitochondrial Zn²⁺ , promoting dynamin-related protein-1 (DRP-1) recruitment and mitochondrial fission. DRP-1-dependent fission via voltage-dependent anion channel 1 (VDAC1)/hexokinase 2 (HK2)-mediated mitochondrial permeability transition pore (mPTP) opening triggered cytochrome c release, activating the intrinsic apoptotic pathway in keratinocytes and contributing to SJS/TEN pathogenesis. 

Investigators identified the galectin-7/TRPM2/Zn²⁺ /DRP-1 pathway as a potential therapeutic target for mitigating SJS/TEN. 

Source: onlinelibrary.wiley.com/doi/full/10.1111/all.16510