Related Experiment Video

Updated: Mar 10, 2026

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

7.8K

Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease

Naoki Nakagawa1,2,3, Luke Barron4, Ivan G Gomez1,2,4

  • 1Division of Nephrology, Departments of Medicine and Pathology, and.

JCI Insight
|December 13, 2016
PubMed

Insights

Pentraxin-2 (PTX-2) therapy slowed chronic kidney disease progression in Alport syndrome mice. This anti-inflammatory protein reduced kidney failure markers and improved survival by inhibiting pathological c-Jun signaling.

Area of Science:

  • Immunology
  • Nephrology
  • Molecular Biology

Background:

  • Pentraxin-2 (PTX-2), or serum amyloid P component (SAP/APCS), is an anti-inflammatory protein with decreased levels in fibrotic diseases.
  • Chronic kidney disease (CKD) is a progressive condition often associated with inflammation and fibrosis.

Purpose of the Study:

  • To investigate the therapeutic potential of recombinant human PTX-2 (rhPTX-2) in a mouse model of Alport syndrome-associated CKD.
  • To elucidate the molecular mechanisms underlying PTX-2's effects on kidney disease progression.

Main Methods:

  • Treatment of Col4a3 mutant mice (Alport syndrome model) with rhPTX-2.
  • Assessment of kidney function, lifespan, and histology.
  • Analysis of rhPTX-2 distribution in kidney tissues.
  • Computational analysis of gene expression and validation of c-Jun/AP-1 pathway modulation.

Main Results:

  • rhPTX-2 administration significantly retarded CKD progression, reduced kidney failure markers, and increased lifespan by 20%.
  • rhPTX-2 localized to macrophages and tubular epithelial cells, exerting anti-inflammatory and cytoprotective effects.
  • PTX-2 was found to attenuate c-Jun and activator protein-1 (AP-1) activity, reducing AP-1-dependent inflammatory gene expression.

Conclusions:

  • rhPTX-2 demonstrates therapeutic potential for chronic fibrotic kidney diseases like Alport syndrome.
  • PTX-2 acts by inhibiting pathological c-Jun/AP-1 signaling in both immune and epithelial cells within the kidney.

More Related Videos

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

7.8K
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

1.0K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.5K
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...
10.8K
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...
9.0K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
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...
7.7K