What question did this study set out to answer?

To determine the role and molecular mechanisms of TRIM72 in pressure overload-induced cardiac fibrosis.

February 28, 2019Journal of Cellular Physiology

TRIM72 contributes to cardiac fibrosis via regulating STAT3/Notch‐1 signaling

View Full Paper

Ask AI

Bookmark

Why the study?

Mechanisms relevant to excessive deposition of extracellular matrix in cardiac fibrosis remain to be uncovered.

Key Points

To determine the role and molecular mechanisms of TRIM72 in pressure overload-induced cardiac fibrosis.
Established a mouse model of cardiac hypertrophy and fibrosis using transverse aortic constriction (TAC) with in vivo shRNA-mediated silencing of TRIM72.
Investigated cardiac fibroblast proliferation, migration, and phenotypic transition in vitro under TRIM72 knockdown, TRIM72 overexpression, and Notch-1 pathway inhibition conditions.
In vivo knockdown of TRIM72 reversed TAC-induced cardiac fibrosis, significantly elevating left ventricular systolic pressure, reducing left ventricular end-diastolic pressure, and decreasing collagen type I and α-SMA deposition.
In vitro, TRIM72 overexpression promoted cardiac fibroblast proliferation, migration, and fibrosis marker expression, whereas TRIM72 silencing suppressed these activities.
TRIM72 increased phosphorylated STAT3 levels, while TRIM72 silencing upregulated Jagged-1 and Notch-1 intracellular domain; pharmacological inhibition of Notch-1 abolished the antifibrotic protection conferred by TRIM72 knockdown.

Structured PICO

Population

Mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and in vitro cardiac fibroblasts

Intervention

In vivo silencing of TRIM72 (knockdown) and in vitro knockdown or overexpression of TRIM72

Outcome

Cardiac fibrosis, indicated by left ventricular systolic and end-diastolic pressures, collagen type I and α-SMA expression, and fibroblast proliferation and migrationsurrogate

TRIM72 promotes cardiac fibrosis and fibroblast-to-myofibroblast transition via the STAT3/Notch-1 pathway, highlighting a potential novel therapeutic target for cardiac remodeling.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

TRIM72 silencing attenuates fibrosis in TAC mice; hypothesis-generating for human cardiac remodeling therapies.

Cite This Study

Chen et al. (2019) studied this question.

synapsesocial.com/papers/6a73d238392fb42db7bcf0f3 https://doi.org/10.1002/jcp.28400

View Full Paper

Ask AI

Bookmark

TRIM72 contributes to cardiac fibrosis via regulating STAT3/Notch‐1 signaling

Key Points

Structured PICO

Discussion

Implication

Cite This Study

TRIM72 contributes to cardiac fibrosis via regulating STAT3/Notch‐1 signaling

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider