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Peer-reviewedCC BY-NC-NDCell communication and signaling : CCS

SFPQ/S100A8 complex induces filaggrin deficiency via selective autophagy and JNK phosphorylation in atopic dermatitis.

  • Geunyeong Kim1
  • Yujin Hong1
  • Tae Young Han2
  • Byeol Han3
  • Beom Seok Park4
  • Eun Ju Yang5
  • Ayesha Kashif1
  • Young Joon Jun6
  • Hongchan An7
  • Juram Lee1
  • Ji Sook Lee8
  • In Sik Kim9,10
10 affiliations
  1. 1Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea.
  2. 2Department of Dermatology, Nowon Eulji Medical Center, Eulji University, Seoul, 01830, Republic of Korea.
  3. 3Department of Dermatology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, 11759, Republic of Korea.
  4. 4Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam, 13135, Republic of Korea.
  5. 5Department of Biomedical Laboratory Science, Daegu Haany University, Gyeongsan, 38610, Republic of Korea.
  6. 6Department of Otorhinolaryngology-Head and Neck Surgery, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, 11759, Republic of Korea.
  7. 7College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon, 11160, Republic of Korea.
  8. 8Department of Biomedical Laboratory Science, College of Healthcare and Medical Sciences, Wonkwang University, Iksan, 54538, Republic of Korea. [email protected].
  9. 9Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea. [email protected].
  10. 10Department of Biomedical Laboratory Science, College of Health Science, Eulji University, 712, Dongil-ro, Uijeongbu, 11759, Republic of Korea. [email protected].
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Abstract

Background

Although atopic dermatitis (AD) is associated with a decrease of filaggrin levels, the underlying mechanisms are not clearly understood. Here, we aimed to investigate the pathogenic roles of the splicing factor proline- and glutamine-rich (SFPQ)/S100 calcium-binding protein A8 (S100A8) complex, a critical regulator inducing filaggrin deficiency in AD.Methods

The formation of SFPQ/S100A8 complex was analyzed in the keratinocytes and skin tissues from patients with AD and 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mice. The effects of leptomycin B, a CRM1 inhibitor, and rapamycin, a mTOR inhibitor were determined in DNCB-induced AD-like mice and the non-lesional and lesional primary keratinocytes of AD patients.Results

The relocation of SFPQ from the nucleus to the cytoplasm, elevated S100A8 levels, and SFPQ/S100A8 complex formation were proportional to filaggrin deficiency and AD severity in the keratinocytes of AD patients and AD-like mice. Interaction of the complex with filaggrin and c-Jun N-terminal kinase (JNK) accelerated filaggrin degradation via selective autophagy and filaggrin downregulation via JNK phosphorylation, respectively. The mechanistic target of rapamycin kinase (mTOR) and chromosomal region maintenance 1 (CRM1) facilitated the cytosolic export of SFPQ to form the complex in human keratinocytes. Administration of leptomycin B and rapamycin suppressed the decrease in filaggrin levels by inhibiting SFPQ/S100A8 complex formation in AD-like mice.Conclusions

This study demonstrates that the formation of SFPQ/S100A8 complex is a critical process in AD progression, which provides key insights into the pathogenic mechanisms of AD. The elucidation of the SFPQ/S100A8 complex axis in AD pathogenesis can be leveraged to develop therapeutic drugs for AD treatment.

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Cite

BibTeXRIS
BibTeX
@article{kim2026sfpqs100a8,
  title = {{SFPQ/S100A8 complex induces filaggrin deficiency via selective autophagy and JNK phosphorylation in atopic dermatitis.}},
  author = {Geunyeong Kim and Yujin Hong and Tae Young Han and Byeol Han and Beom Seok Park and Eun Ju Yang and Ayesha Kashif and Young Joon Jun and Hongchan An and Juram Lee and Ji Sook Lee and In Sik Kim},
  journal = {Cell communication and signaling : CCS},
  year = {2026},
  month = jul,
  doi = {10.1186/s12964-026-02776-5},
  url = {https://europepmc.org/article/MED/42897640},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - SFPQ/S100A8 complex induces filaggrin deficiency via selective autophagy and JNK phosphorylation in atopic dermatitis.
AU  - Geunyeong Kim
AU  - Yujin Hong
AU  - Tae Young Han
AU  - Byeol Han
AU  - Beom Seok Park
AU  - Eun Ju Yang
AU  - Ayesha Kashif
AU  - Young Joon Jun
AU  - Hongchan An
AU  - Juram Lee
AU  - Ji Sook Lee
AU  - In Sik Kim
PY  - 2026
DA  - 2026/07/01
JO  - Cell communication and signaling : CCS
DO  - 10.1186/s12964-026-02776-5
UR  - https://europepmc.org/article/MED/42897640
AB  - Background  Although atopic dermatitis (AD) is associated with a decrease of filaggrin levels, the underlying mechanisms are not clearly understood. Here, we aimed to investigate the pathogenic roles of the splicing factor proline- and glutamine-rich (SFPQ)/S100 calcium-binding protein A8 (S100A8) complex, a critical regulator inducing filaggrin deficiency in AD.Methods  The formation of SFPQ/S100A8 complex was analyzed in the keratinocytes and skin tissues from patients with AD and 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mice. The effects of leptomycin B, a CRM1 inhibitor, and rapamycin, a mTOR inhibitor were determined in DNCB-induced AD-like mice and the non-lesional and lesional primary keratinocytes of AD patients.Results  The relocation of SFPQ from the nucleus to the cytoplasm, elevated S100A8 levels, and SFPQ/S100A8 complex formation were proportional to filaggrin deficiency and AD severity in the keratinocytes of AD patients and AD-like mice. Interaction of the complex with filaggrin and c-Jun N-terminal kinase (JNK) accelerated filaggrin degradation via selective autophagy and filaggrin downregulation via JNK phosphorylation, respectively. The mechanistic target of rapamycin kinase (mTOR) and chromosomal region maintenance 1 (CRM1) facilitated the cytosolic export of SFPQ to form the complex in human keratinocytes. Administration of leptomycin B and rapamycin suppressed the decrease in filaggrin levels by inhibiting SFPQ/S100A8 complex formation in AD-like mice.Conclusions  This study demonstrates that the formation of SFPQ/S100A8 complex is a critical process in AD progression, which provides key insights into the pathogenic mechanisms of AD. The elucidation of the SFPQ/S100A8 complex axis in AD pathogenesis can be leveraged to develop therapeutic drugs for AD treatment.
SN  - 1478-811X
ER  -