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Review
. 2024 Jun:97:102314.
doi: 10.1016/j.arr.2024.102314. Epub 2024 Apr 24.

Senescence-associated secretory phenotype (SASP) and uterine fibroids: Association with PD-L1 activation and collagen deposition

Eslam E Saad  1 , Rachel Michel  2 , Mostafa A Borahay  3
Affiliations
Review

Senescence-associated secretory phenotype (SASP) and uterine fibroids: Association with PD-L1 activation and collagen deposition

Eslam E Saad et al. Ageing Res Rev. 2024 Jun.

Abstract

Uterine fibroids (or uterine leiomyoma, UFs) are one of the most prevalent benign uterine tumors with high proliferation and collagen synthesis capabilities. UFs are a significant worldwide health issue for women, affecting their physical and financial well-being. Risk factors for UFs include age, racial disparities, obesity, uterine infections, hormonal variation, and lifestyle (i.e., diet, exercise, stress, and smoking). Senescence and its associated secretory phenotypes (SASPs) are among the most salient changes accompanying the aging process. As a result, SASPs are suggested to be one of the major contributors to developing UFs. Interleukin 6 (IL-6), IL-8, IL-1, chemokine ligand 20 (CCL-20), and transforming growth factor-beta (TGF-β) are the most prominent SASPs associated with aging. In addition, different processes contribute to UFs such as collagen deposition and the changes in the immune microenvironment. Programmed death ligand 1 is a major player in the tumor immune microenvironment, which helps tumor cells evade immune attacks. This review focuses on the correlation of SASPs on two axes of tumor progression: immune suppression and collagen deposition. This review opens the door towards more investigations regarding changes in the UF immune microenvironment and age-UFs correlation and thus, a novel targeting approach for UF treatment.

Keywords: Collagen; PD-L1; SASPs; Uterine Fibroids.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1:
Figure 1:
Effect of SASPs on UFs. SASPs induce UF by affecting proliferation and collagen synthesis.
Figure 2:
Figure 2:. Effect Of IL-6 on PD-L1 and collagen levels.
IL-6 induces the PD-L1 effect through four different mechanisms; (1) It stimulates STT3A which increases PD-L1 Glycosylation and thus its stability, (2) It activates PD-L1 gene expression through JAK2/STAT1, (3) It activates PD-L1 gene expression through JAK2/STAT3/MYC, and (4) It inhibits the effect of Anti-PD-L1 and thus potentiates PD-L1. IL-6 also was found to increase collagen levels.
Figure 3:
Figure 3:. Effect Of IL-8 on PD-L1 and collagen levels.
IL-8 induces the PD-L1 effect either directly or through C-MYC. IL-8 also was found to increase collagen levels mainly through PI3K/AKT.
Figure 4:
Figure 4:. Effect of IL-1 on PD-L1 and Collagen synthesis in UFs.
IL-1 increases PD-L1 through activation of NF-kB or SLC7A11. IL-1 also increases collagen synthesis through IL-17A and enhances fibroblast to myofibroblast transformation.
Figure 5:
Figure 5:
Effect of CCL-20 on PD-L1 and Collagen synthesis in UFs.
Figure 6:
Figure 6:
Effect of CCL-20 on PD-L1 and Collagen Synthesis in UFs.
See this image and copyright information in PMC

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