Related Experiment Video

Updated: Oct 5, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

The involvement of p38 MAPK in transforming growth factor beta1-induced apoptosis in murine hepatocytes

J H Liao1, J S Chen, M Q Chai

  • 1State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai.

Cell Research
|July 17, 2001
PubMed

Insights

Transforming growth factor-beta1 (TGF-β1) triggers apoptosis in liver cells via p38 mitogen-activated protein kinase (MAPK) pathway activation. Inhibiting p38 MAPK blocks this TGF-β1-induced cell death and gene expression.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cell Signaling

Background:

  • Transforming growth factor-beta1 (TGF-β1) is a key regulator of cellular processes, including apoptosis.
  • The role of specific signaling pathways, such as p38 MAPK, in TGF-β1-induced hepatocyte apoptosis requires further elucidation.

Purpose of the Study:

  • To investigate the involvement of the p38 MAPK signaling pathway in TGF-β1-induced apoptosis of AML12 murine hepatocytes.
  • To determine the effect of p38 MAPK inhibition on TGF-β1-mediated gene expression.

Main Methods:

  • AML12 murine hepatocytes were treated with TGF-β1.
  • Apoptosis was assessed, and p38 MAPK activation was measured.
  • SB202190, a p38 MAPK inhibitor, and dominant-negative p38 mutant were used to evaluate pathway involvement.
  • PAI-1 promoter activity was analyzed.

Main Results:

  • TGF-β1 treatment induced apoptosis in AML12 hepatocytes.
  • TGF-β1 activated the p38 MAPK signaling pathway.
  • SB202190 significantly inhibited TGF-β1-induced apoptosis and PAI-1 promoter activity.
  • Overexpression of dominant-negative p38 mutant reduced TGF-β1-induced apoptosis.

Conclusions:

  • Activation of the p38 MAPK pathway is critical for TGF-β1-induced apoptosis in murine hepatocytes.
  • The p38 MAPK pathway mediates TGF-β1-induced gene expression, including PAI-1.
  • Targeting the p38 MAPK pathway may offer therapeutic potential in conditions involving TGF-β1-mediated liver injury.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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 are of three kinds RI, RII, and RIII. The RI...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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 rapamycin-insensitive companion...