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FOXA1 transcription activates TFF1 to reduce 6-OHDA-induced dopaminergic neuron damage

Tingting Liang1, Ping Zhao1, Xiao Zhang1

  • 1Department of Neurology, The Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University, Lianyungang, Jiangsu 222042, P.R. China.

Experimental and Therapeutic Medicine
|May 2, 2022
PubMed

Insights

Forkhead box A1 (FOXA1) is downregulated in Parkinson's disease (PD). Overexpressing FOXA1 reduces inflammation, oxidative stress, and apoptosis in PD models by activating trefoil factor 1 (TFF1).

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Forkhead box A1 (FOXA1) is crucial in the central nervous system and linked to dopamine synthesis.
  • Downregulation of FOXA1 affects tyrosine hydroxylase, impacting dopamine synthesis and potentially leading to Parkinson's disease (PD).

Purpose of the Study:

  • To investigate the specific role of FOXA1 in Parkinson's disease (PD).
  • To explore the therapeutic potential of FOXA1 in PD treatment.

Main Methods:

  • Examined FOXA1 expression in PD patients' blood via RT-qPCR.
  • Utilized a 6-hydroxydopamine (6-OHDA) induced in vitro PD model using MES23.5 cells.
  • Assessed FOXA1 overexpression effects on inflammation, oxidative stress, and apoptosis using RT-qPCR, assay kits, and TUNEL assays.
  • Investigated FOXA1's downstream mechanism, including binding to the trefoil factor 1 (TFF1) promoter and effects of TFF1 silencing.

Main Results:

  • FOXA1 expression was significantly downregulated in patients with PD.
  • Overexpression of FOXA1 attenuated 6-OHDA-induced inflammation, oxidative stress, and apoptosis in MES23.5 cells.
  • FOXA1 directly binds to the TFF1 promoter, and TFF1 silencing reversed the protective effects of FOXA1 overexpression.
  • FOXA1 activates TFF1 transcription, which in turn alleviates 6-OHDA-induced cellular damage.

Conclusions:

  • FOXA1 plays a protective role in PD by reducing inflammation, oxidative stress, and apoptosis.
  • The mechanism involves FOXA1-mediated transcriptional activation of TFF1.
  • FOXA1 represents a potential therapeutic target for Parkinson's disease.
Keywords:
6-hydroxydopamineMES23.5 cellsParkinson's diseaseforkhead box A1trefoil factor 1

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