Mitomycin induces alveolar epithelial cell senescence by down-regulating GSK3β signaling

Xu, Xiafang; Sun, Xiaoyan; Wan, Xuelei; Chen, Xihua; Jiang, Xiaogang

doi:10.1016/j.toxlet.2021.09.015

Cited by 7 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increased AF in DNA-damage-induced senescent MearF was additionally confirmed by treatment with MMC (75 nM for 1 week). Indeed, MMC does not display intrinsic AF visible in the Ch02 channel ( Supplementary Figure S6 ) and, similarly to DOX, is known to induce senescence by DNA damage [ 21 ]. As expected, samples treated with MMC showed a mean increase in AF intensity above 3000 ( Supplementary Figure S6 ), similar to the results observed with DOX ( Figure 2 a), thus confirming that the increased AF of senescent MearF is due to processes associated with senescence rather than to the intrinsic properties of the drug.…”

Section: Resultsmentioning

confidence: 99%

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Malavolta

Giacconi

Piacenza

et al. 2022

Cells

View full text Add to dashboard Cite

Cellular senescence is a hallmark of aging and a promising target for therapeutic approaches. The identification of senescent cells requires multiple biomarkers and complex experimental procedures, resulting in increased variability and reduced sensitivity. Here, we propose a simple and broadly applicable imaging flow cytometry (IFC) method. This method is based on measuring autofluorescence and morphological parameters and on applying recent artificial intelligence (AI) and machine learning (ML) tools. We show that the results of this method are superior to those obtained measuring the classical senescence marker, senescence-associated beta-galactosidase (SA-β-Gal). We provide evidence that this method has the potential for diagnostic or prognostic applications as it was able to detect senescence in cardiac pericytes isolated from the hearts of patients affected by end-stage heart failure. We additionally demonstrate that it can be used to quantify senescence “in vivo” and can be used to evaluate the effects of senolytic compounds. We conclude that this method can be used as a simple and fast senescence assay independently of the origin of the cells and the procedure to induce senescence.

show abstract

Section: Resultsmentioning

confidence: 99%

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Malavolta

Giacconi

Piacenza

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Moreover, p21, a downstream target of p53, directly induces cellular senescence ( 66 ). Similarly, senescence of alveolar epithelial cells can be induced by increasing GSK-3β phosphorylation ( 67 ). In addition, activated β-catenin signaling triggers DNA damage response (DDR) ( 68 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of alveolar epithelial cell senescence and idiopathic pulmonary fibrosis: a narrative review

Tu¹,

Wei²,

Jia³

et al. 2023

J Thorac Dis

View full text Add to dashboard Cite

Background and Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia of unknown etiology. An increasing number of studies have reported that the incidence of IPF increases with age. Simultaneously, the number of senescent cells increased in IPF. Epithelial cell senescence, an important component of epithelial cell dysfunction, plays a key role in IPF pathogenesis. This article summarizes the molecular mechanisms associated with alveolar epithelial cell senescence and recent advances in the applications of drugs targeting pulmonary epithelial cell senescence to explore novel therapeutic approaches for the treatment of pulmonary fibrosis.Methods: All literature published in English on PubMed, Web of Science, and Google Scholar were electronically searched online using the following keyword combinations: aging, alveolar epithelial cell, cell senescence, idiopathic pulmonary fibrosis, WNT/β-catenin, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB).

show abstract

“…To date, it has been demonstrated in primary and immortalized cultures (human dermal fibroblasts; alveolar epithelial cells; non-small-cell lung cancer-A549 cells; and primary and telomerase immortalized human corneal limbal epithelial cells) that MmC-treated cells display characteristics of senescent cells, such as abrogated proliferation, a stable change in cell morphology, intensified senescence-associated β-galactosidase (SA-β-gal) activity, and a transient increase in the ROS level, upregulated SASP factors, p21, p53, retinoblastoma (Rb) genes, etc. [27][28][29][30]. MmC is an alkylating DNA-damaging agent and ROS producer.…”

Section: Cell Senescence Inductionmentioning

confidence: 99%

Senescence-Associated Alterations in Matrisome of Mesenchymal Stem Cells

Matveeva,

Kashirina,

Ezdakova

et al. 2024

IJMS

View full text Add to dashboard Cite

The process of aging is intimately linked to alterations at the tissue and cellular levels. Currently, the role of senescent cells in the tissue microenvironment is still being investigated. Despite common characteristics, different cell populations undergo distinctive morphofunctional changes during senescence. Mesenchymal stem cells (MSCs) play a pivotal role in maintaining tissue homeostasis. A multitude of studies have examined alterations in the cytokine profile that determine their regulatory function. The extracellular matrix (ECM) of MSCs is a less studied aspect of their biology. It has been shown to modulate the activity of neighboring cells. Therefore, investigating age-related changes in the MSC matrisome is crucial for understanding the mechanisms of tissue niche ageing. This study conducted a broad proteomic analysis of the matrisome of separated fractions of senescent MSCs, including the ECM, conditioned medium (CM), and cell lysate. This is the first time such an analysis has been conducted. It has been established that there is a shift in production towards regulatory molecules and a significant downregulation of the main structural and adhesion proteins of the ECM, particularly collagens, fibulins, and fibrilins. Additionally, a decrease in the levels of cathepsins, galectins, S100 proteins, and other proteins with cytoprotective, anti-inflammatory, and antifibrotic properties has been observed. However, the level of inflammatory proteins and regulators of profibrotic pathways increases. Additionally, there is an upregulation of proteins that can directly cause prosenescent effects on microenvironmental cells (SERPINE1, THBS1, and GDF15). These changes confirm that senescent MSCs can have a negative impact on other cells in the tissue niche, not only through cytokine signals but also through the remodeled ECM.

show abstract

Mitomycin induces alveolar epithelial cell senescence by down-regulating GSK3β signaling

Cited by 7 publications

References 25 publications

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Molecular mechanisms of alveolar epithelial cell senescence and idiopathic pulmonary fibrosis: a narrative review

Senescence-Associated Alterations in Matrisome of Mesenchymal Stem Cells

Contact Info

Product

Resources

About