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Cytoskeletal protein SPTA1 mediating the decrease in erectile function induced by high-fat diet via Hippo signaling

Ying Chen1,2, Lei Wang3, Zhan-Sen Huang1

  • 1Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Andrology
|November 14, 2022
PubMed
Summary
This summary is machine-generated.

High-fat diets decrease erectile function by down-regulating spectrin alpha, erythrocytic 1 (SPTA1), which may trigger cell pyroptosis and activate the Hippo pathway. These findings offer new therapeutic targets for improving erectile function.

Keywords:
Hippo signalling pathwaySPTA1cell pyroptosiserectile function decreasedhigh-fat diet

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Area of Science:

  • Urology
  • Molecular Biology
  • Cell Biology

Background:

  • High-fat diet (HFD)-induced erectile dysfunction mechanisms remain unclear.
  • Spectrin alpha, erythrocytic 1 (SPTA1), a cytoskeletal protein, influences cell growth via the Hippo signaling pathway, but its role in erectile function is unelucidated.

Purpose of the Study:

  • To investigate the role of SPTA1 in HFD-induced erectile dysfunction.

Main Methods:

  • Transcriptomic analysis of penile tissues from mice on normal and HFD.
  • Verification of SPTA1 expression in rat penile tissues and in vitro cell models (high-glucose treated CCECs and CCSMCs).
  • Single-cell sequencing to determine SPTA1 distribution and gene interference to explore mechanisms.

Main Results:

  • SPTA1 was identified as a down-regulated gene in HFD-induced erectile dysfunction.
  • SPTA1 protein expression decreased in HFD rat penile tissues and HG-treated CCECs/CCSMCs.
  • Interfering with SPTA1 in CCSMCs led to eNOS down-regulation and pyroptosis/Hippo pathway activation (YAP, Caspase-1, GSDMD, IL-18, IL-1β up-regulation).

Conclusions:

  • Down-regulation of SPTA1 in HFD may induce pyroptosis and erectile dysfunction via Hippo pathway activation.
  • SPTA1 modulation presents a potential therapeutic strategy for erectile dysfunction.