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Using an Unbiased Coexpression Network to Reveal Cross-Talking Pathways of Phosphoinositide-3-Kinase Regulatory

Zhike Zhou1, Sha Sha1, Xiangnan Zhou2

  • 1Department of Geriatrics, The First Hospital of China Medical University, Shenyang, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 17, 2026
PubMed

Insights

The study found that PIK3R1 (Phosphoinositide 3-kinase regulatory subunit 1) expression decreases with skin aging and after rejuvenation treatments. Lower PIK3R1 levels may protect skin cells from damage, suggesting it as a target for skin rejuvenation therapies.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Genetics

Background:

  • Skin aging is a complex process involving chronological aging and photoaging, with underlying mechanisms still under investigation.
  • Advancements in understanding skin aging drive innovation in rejuvenation therapies, yet key molecular pathways remain underexplored.

Purpose of the Study:

  • To investigate the role of PIK3R1 (Phosphoinositide 3-kinase regulatory subunit 1) in skin aging and rejuvenation.
  • To identify molecular pathways associated with PIK3R1 expression and their impact on skin cell behavior.

Main Methods:

  • Differential gene expression (DEG) analysis and weighted gene correlation network analysis (WGCNA) were employed.
  • Network analysis and pathway enrichment analyses were performed on DEGs related to skin vitality and PIK3R1.
  • RT-PCR and Western blot were used to validate PIK3R1 expression changes. PIK3R1 knockdown experiments were conducted in human dermal fibroblasts (HDFs).

Main Results:

  • PIK3R1 expression was found to decrease gradually in aged skin (both untreated and treated) and young skin compared to aged untreated skin.
  • Coexpression network analysis revealed PIK3R1's association with PI3K/AKT, Rap1, and regulating pluripotency of stem cells (rPSC) pathways.
  • PIK3R1 knockdown in HDFs enhanced resistance to UVA-induced senescence, apoptosis, and collagen decline, potentially via modulation of AKT, Bcl-2, FOXO1, and MMP-1.

Conclusions:

  • PIK3R1 plays a significant role in skin aging and may serve as a predictive marker for skin aging and rejuvenation.
  • The findings suggest PIK3R1's involvement in key cellular pathways regulating skin vitality and response to aging and rejuvenation stimuli.
  • PIK3R1 presents a potential novel therapeutic target for developing effective skin rejuvenation strategies.
Keywords:
co‐expression networkdifferentially expressed genesphosphoinositide‐3‐kinase regulatory subunit 1skin agingskin rejuvenation

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