Related Experiment Video

Updated: May 31, 2025

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

8.1K

Downregulated TFPI2 Accelerates Skin Aging by Repressing the Cell Cycle through Phosphoinositide 3-Kinase/Protein

Fan Wang1, Caitan Yi1, Yun Zhong2

  • 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

The Journal of Investigative Dermatology
|January 23, 2025
PubMed

Insights

Tissue Factor Pathway Inhibitor 2 (TFPI2) counteracts skin aging by maintaining cell cycle progression. Lower TFPI2 levels accelerate skin aging, but its activation offers potential antiaging interventions.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • Tissue Factor Pathway Inhibitor 2 (TFPI2) regulates cell proliferation but its role in skin aging is unknown.
  • Skin aging involves cellular senescence and changes in tissue characteristics.

Purpose of the Study:

  • To investigate the role of TFPI2 in skin aging.
  • To identify the molecular mechanisms underlying TFPI2's function in skin aging.

Main Methods:

  • Analysis of TFPI2 expression in aging skin and fibroblasts.
  • RNA sequencing to identify downstream targets of TFPI2.
  • Liquid chromatography-mass spectrometry to confirm protein interactions.
  • Functional assays to assess the impact of TFPI2 on cell senescence and cell cycle.

Main Results:

  • TFPI2 expression is reduced in aging skin and senescent fibroblasts.
  • TFPI2 depletion accelerates skin aging and fibroblast senescence.
  • TFPI2 targets CDC6, a cell cycle regulator.
  • TFPI2 activates the PI3K/Akt pathway via interaction with p85β, promoting CDC6 expression and cell cycle progression, thereby alleviating senescence.

Conclusions:

  • TFPI2 acts as an antagonist of skin aging.
  • The TFPI2/PI3K/Akt/CDC6 pathway is crucial for regulating skin aging.
  • Targeting this pathway holds promise for developing novel antiaging therapies.
Keywords:
CDC6Cellular senescencePI3K/AktSkin agingTFPI2

More Related Videos

Techniques to Induce and Quantify Cellular Senescence06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

33.1K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.7K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.1K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K