ArticleOrphanet journal of rare diseases2023
PAI1 inhibits the pathogenesis of primary focal hyperhidrosis by targeting CHRNA1.
Article in Orphanet journal of rare diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 4 citations in OpenAlex.
- Primary Hyperhidrosis: A Review of Epidemiology, Pathophysiology and Management.Acta dermato-venereologica · 2026Review
- PAI-1 and CHRNA1-A new molecular axis and therapeutic target in primary focal hyperhidrosis.Molecular therapy. Nucleic acids · 2025Article
- PAI1 regulating CHRNA1 contributes to primary focal hyperhidrosis: Clinical and experimental studies.Molecular therapy. Nucleic acids · 2025Article
- Polydatin ameliorates hyperhidrosis by targeting Aqp5 in a mouse model.Frontiers in pharmacology · 2025Article
- Altered Th17/Treg balance and therapeutic targeting of RORγ in primary focal hyperhidrosis.Frontiers in immunology · 2025Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrimary focal hyperhidrosis (PFH) may be attributed to the up-regulation of the cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in eccrine glands. Plasminogen activator inhibitor-1 (PAI1, encoded by SERPINE1) is reported to inhibit the expression of CHRNA1, while the role of PAI1 in hyperhidrosis is unknown.
methodsSerpine1 KO mice, Serpine1-Tg mice, and wild type BALB/c mice were intraperitoneally injected with pilocarpine hydrochloride to induce PFH. Cisatracurium (CIS, antagonist of CHRNA1) or PAI-039 (small-molecule inhibitor of PAI1) was pre-administrated before the induction of hyperhidrosis. On the other hand, Chrna1-expressing AAV was constructed and administered to Serpine1-Tg mice with hydrochloride stimulation. Hydrochloride-related biomarkers, such as acetylcholine (ACH) in the serum, calcium voltage-gated channel subunit alpha1 C (CACNA1C), and aquaporin 5 (AQP5) in sweat glands of mice were assayed with ELISA, RT-PCR, and Western blot.
resultsThe administration of PAI-039 or Pai1 knock-out increased Chrna1 expression, sweat secretion, and hydrochloride-related biomarkers (ACH, CACNA1C, and AQP5) expression. On the other hand, CIS administration diminished the strengthened hyperhidrosis phenotype induced by Pai1 knock-out with decreased sweat gland secretion.
conclusionPAI1 inhibits CHRNA1-mediated hydrochloride-induced hyperhidrosis, with decreased sweat gland secretion and diminished ACH, AQP5, and CACNA1C expression. These results indicate the potential to utilize PAI1 to alleviate PFH.
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