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Updated: Oct 29, 2025

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
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A Negative Feedback Loop in Ultraviolet A-Induced Senescence in Human Dermal Fibroblasts Formed by SPCA1 and MAPK

Hongfu Xie1, Xiao Xiao2, Yuxin Yi1

  • 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Cell and Developmental Biology
|July 9, 2021
PubMed

Insights

Secretory pathway calcium ATPase 1 (SPCA1) protects against UVA-induced skin cell aging. Upregulating SPCA1 reduces calcium overload, reactive oxygen species, and MAPK activity, thereby alleviating senescence.

Area of Science:

  • Cell Biology
  • Dermatology
  • Biochemistry

Background:

  • Cellular senescence is a key factor in skin aging.
  • UVA irradiation is a major environmental contributor to skin aging and damage.
  • The role of Secretory pathway calcium ATPase 1 (SPCA1) in UVA-induced senescence was previously unknown.

Purpose of the Study:

  • To investigate the role of SPCA1 in human dermal fibroblasts (HDFs) undergoing UVA-induced senescence.
  • To elucidate the molecular mechanisms by which SPCA1 influences UVA-induced cellular aging.

Main Methods:

  • Human dermal fibroblasts (HDFs) were irradiated with UVA.
  • SPCA1 expression was modulated using siRNA and overexpression.
  • Mitogen-activated protein kinase (MAPK) and c-jun activation were assessed.
  • Intracellular calcium levels and reactive oxygen species (ROS) were measured.
  • Dual-luciferase reporter and chromatin immunoprecipitation assays were performed.

Main Results:

  • UVA irradiation increased SPCA1 expression via MAPK/c-jun signaling.
  • c-jun directly regulated SPCA1 promoter activity.
  • Downregulating SPCA1 exacerbated UVA-induced senescence by increasing intracellular calcium, ROS, and MAPK activity.
  • Overexpressing SPCA1 alleviated senescence by reducing calcium overload, ROS, and MAPK activation.

Conclusions:

  • SPCA1 plays a protective role against UVA-induced senescence in HDFs.
  • SPCA1 functions within a negative feedback loop involving MAPK/c-jun signaling.
  • SPCA1 mitigates cellular damage by regulating intracellular calcium homeostasis, reducing ROS production, and suppressing MAPK activity.
Keywords:
MAPK pathwayROSSPCA1UVAintracellular calcium concentrationnegative feedback

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