Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.5K
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...
3.5K
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Timp2 Protects Against Sepsis-associated Acute Kidney Injury By Camp/nlrp3 Axis-mediated Pyroptosis.

TIMP2 protects against sepsis-associated acute kidney injury by cAMP/NLRP3 axis-mediated pyroptosis.

Dongxue Xu1, Jun Jiang1, Ye Liu1

  • 1Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.

American Journal of Physiology. Cell Physiology
|March 18, 2024

Related Experiment Videos

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
06:40

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

28.4K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.2K
Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

1.9K

View abstract on PubMed

Summary
This summary is machine-generated.

Tissue inhibitor of metalloproteinases 2 (TIMP2) protects kidneys from sepsis-associated acute kidney injury (SA-AKI). TIMP2 reduces tubular pyroptosis by degrading NLRP3, suggesting its therapeutic potential for SA-AKI.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Sepsis-associated acute kidney injury (SA-AKI) poses a significant clinical challenge.
  • Tissue inhibitor of metalloproteinases 2 (TIMP2) is a recognized biomarker for SA-AKI risk.
  • The precise role and molecular mechanisms of TIMP2 in SA-AKI pathogenesis are not fully understood.

Purpose of the Study:

  • To elucidate the functional role of TIMP2 in kidney injury during SA-AKI.
  • To investigate the underlying molecular mechanisms by which TIMP2 influences SA-AKI.
  • To assess the therapeutic potential of exogenous TIMP2 in SA-AKI.

Main Methods:

  • Generation and analysis of kidney tubule-specific Timp2 knockout mice.
  • In vitro studies using primary renal tubular cells stimulated with lipopolysaccharide (LPS).
Keywords:
AKINLRP3 inflammasomePyroptosisSepsis

Related Experiment Videos

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
06:40

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

28.4K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.2K
Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

1.9K
  • Assessment of kidney injury, inflammation, pyroptosis markers (NLRP3, Caspase1, GSDMD), and TIMP2 expression.
  • Investigation of TIMP2-mediated NLRP3 degradation pathways involving cAMP, ubiquitination, and autophagy.

    • Main Results:

    • Timp2-knockout mice exhibited exacerbated kidney injury and elevated pyroptosis markers during early SA-AKI.
    • Exogenous TIMP2 administration protected against kidney damage and inflammation in knockout mice.
    • In vitro, recombinant TIMP2 inhibited LPS-induced pyroptosis in renal tubular cells.
    • TIMP2 enhanced NLRP3 ubiquitination and autophagy-dependent degradation via increased intracellular cAMP, recruiting MARCH7.

    Conclusions:

    • Extracellular TIMP2 exerts a renoprotective effect in SA-AKI by attenuating tubular pyroptosis.
    • TIMP2's mechanism involves promoting NLRP3 degradation through the cAMP-autophagy-ubiquitination pathway.
    • Exogenous TIMP2 represents a promising therapeutic strategy for treating SA-AKI.
    TIMP2