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Updated: Mar 21, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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The PKA/MBD2 Axis Transcriptionally Represses INPP5A to Modulate PI3K/Akt Signaling and Accelerate Pituitary

Qian Jiang1,2, Yaorui Wang1,2, Zihan Wang1,2

  • 1Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei province, China.

CNS Neuroscience & Therapeutics
|March 20, 2026
PubMed
Abstract

Insights

Inositol polyphosphate 5-phosphatase A (INPP5A) suppresses pituitary neuroendocrine tumor (PitNET) growth by inhibiting the PI3K/Akt pathway. Its downregulation promotes malignancy, with MBD2 mediating repression.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Malignant progression of pituitary neuroendocrine tumors (PitNETs) is linked to phosphoinositide pathway dysregulation.
  • Inositol polyphosphate 5-phosphatase A (INPP5A) role in PitNETs is unclear.

Purpose of the Study:

  • Investigate INPP5A's regulatory role in PitNET malignant progression.
  • Elucidate INPP5A's mechanism involving the PI3K/Akt pathway and MBD2.

Main Methods:

  • Analyzed IP3 metabolism genes in PitNET single-cell sequencing data (NCBI).
  • Performed immunofluorescence and statistical analysis on 62 PitNET patient samples.

Main Results:

  • INPP5A was downregulated in PitNETs, correlating inversely with invasiveness and proliferation markers.
  • INPP5A overexpression inhibited, while knockdown promoted, PitNET cell malignant phenotypes.
  • INPP5A negatively regulated PI3K/Akt by degrading IP3; MBD2 repressed INPP5A transcription.
  • PKA-mediated MBD2 phosphorylation stabilized MBD2, enhancing INPP5A repression.

Conclusions:

  • INPP5A functions as a tumor suppressor in PitNETs, with downregulation activating PI3K/Akt.
  • MBD2 and PKA-mediated phosphorylation are key to INPP5A transcriptional repression.
  • The MBD2-INPP5A-PI3K/Akt axis presents a potential therapeutic target for PitNETs.
Keywords:
14–3‐3σINPP5AMBD2PKAPitNET

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