Acute downregulation of miR-155 leads to a reduced collagen synthesis through attenuating macrophages inflammatory factor secretion by targeting SHIP1
Related Experiment Video
Updated: Feb 15, 2026
Neuron-Macrophage Co-cultures to Activate Macrophages Secreting Molecular Factors with Neurite Outgrowth Activity
Published on: March 30, 2018
Longlong Yang1, Lingying Liu1, Huinan Ying1
1Department of Burn & Plastic Surgery, Burns Institute, the First Affiliated Hospital to PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
Abstract:
Fibrosis, tightly associated with fibroblasts collagen synthesis, is related closely with inflammatory response. Our previously study found that acute downregulation of miR-155 at wound sites leads to a reduced fibrosis, however its particular mechanism is unclear. Herein, we aimed to explore the mechanism of miR-155 in reducing fibrosis. We first found that down-regulation of miR-155 inhibited macrophages transforming growth factor-β1 (TGF-β1) and IL-1β secretion. Next, we found that co-cultured with macrophages increased the proliferation and collagen synthesis of fibroblasts, and downregulation of miR-155 in macrophages could effectively attenuate the accelerative effects. We further identified SH2 domain containing inositol-5-phosphatase 1 (SHIP1) as a direct target of miR-155 in macrophages, and the expression of SHIP1 was negatively correlated with the level of miR-155. We further confirmed that PI3K/Akt pathway was involved in this process. Last, we found that downregulation of miR-155 leads to a reduced fibrosis in sever burn rat. Taken together, these results indicate that down-regulation of miR-155 leads to a reduced fibroblasts proliferation and collagen synthesis through attenuating macrophages TGF-β1 and IL-1β secretion by targeting SHIP1 via PI3K/Akt pathway, suggesting its potential therapeutic effects on the treatment of skin fibrosis.
Insights
Downregulating miR-155 reduces skin fibrosis by inhibiting inflammatory factors and fibroblast activity. This occurs via targeting SHIP1 and the PI3K/Akt pathway in macrophages, offering potential therapeutic benefits.
Area of Science:
- * Molecular Biology
- * Immunology
- * Dermatology
Background:
- * Fibrosis, characterized by fibroblast collagen synthesis, is closely linked to inflammatory responses.
- * Previous studies indicated acute downregulation of miR-155 reduces fibrosis at wound sites, but the mechanism remains unclear.
- * Understanding miR-155's role is crucial for developing targeted fibrosis therapies.
Purpose of the Study:
- * To elucidate the mechanism by which miR-155 downregulation reduces fibrosis.
- * To investigate the impact of miR-155 on macrophage-derived inflammatory factors.
- * To identify the molecular targets and pathways involved in miR-155's antifibrotic effects.
Main Methods:
- * Investigated the effect of miR-155 downregulation on macrophage secretion of TGF-β1 and IL-1β.
- * Assessed the impact of macrophage-fibroblast co-culture on fibroblast proliferation and collagen synthesis.
- * Identified SHIP1 as a direct target of miR-155 in macrophages and analyzed the PI3K/Akt pathway.
- * Evaluated the effect of miR-155 downregulation on skin fibrosis in a rat burn model.
Main Results:
- * Downregulation of miR-155 inhibited TGF-β1 and IL-1β secretion from macrophages.
- * Macrophages with downregulated miR-155 showed reduced ability to promote fibroblast proliferation and collagen synthesis.
- * SHIP1 was identified as a direct target of miR-155, with inverse correlation in expression, implicating the PI3K/Akt pathway.
- * Downregulation of miR-155 significantly reduced skin fibrosis in a rat severe burn model.
Conclusions:
- * Down-regulation of miR-155 reduces fibroblast proliferation and collagen synthesis by attenuating macrophage TGF-β1 and IL-1β secretion.
- * The mechanism involves targeting SHIP1 via the PI3K/Akt pathway in macrophages.
- * These findings suggest miR-155 downregulation has potential therapeutic effects for treating skin fibrosis.
More Related Videos
07:44Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
08:34Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
Related Concept Videos
02:42Transcription Attenuation in Prokaryotes
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
02:17Synthesis and Decomposition Reactions
01:59Lagging Strand Synthesis
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
02:16Transcription Factors