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Updated: Sep 26, 2025
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
GDF11 ameliorates severe acute pancreatitis through modulating macrophage M1 and M2 polarization by targeting the
Feixiang Duan1, Xiaowu Wang2, Hongwei Wang1
1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
Abstract:
Severe acute pancreatitis (SAP), as a typical acute inflammatory injury disease, is one of the acute gastrointestinal diseases with a remarkable mortality rate. Macrophages, typical inflammatory cells involved in SAP, play an important role in the pathogenesis of SAP, which are separated into proinflammation M1 and antiinflammation M2. Growth and differentiation factor 11 (GDF11), as a member of the TGF-β family also called BMP-11, has been discovered to suppress inflammation. However, the mechanism by which GDF11 inhibits inflammation and whether it can ameliorate SAP are still elusive. The present research aimed to investigate the roles of GDF11 in SAP and the potential immunomodulatory effect of macrophage polarization. The mouse and rat SAP model were constructed by caerulein and retrograde injection of sodium taurocholate respectively. The effects of GDF11 on SAP were observed by serology, histopathology and tissue inflammation, and the effects of GDF11 on the polarization of macrophages in vivo were observed. Raw264.7 and THP1 crells were used to study the effect of GDF11 on macrophage polarization in vitro. To further investigate the causal link underneath, our team first completed RNA and proteome sequencing, and utilized specific suppressor to determine the implicated signal paths. Herein, we discovered that GDF11 alleviated the damage of pancreatic tissues in cerulein induced SAP mice and SAP rats induced by retrograde injection of sodium taurocholate, and further found that GDF11 facilitated M2 macrophage polarization and diminished M1 macrophage polarization in vivo and in vitro. Subsequently, we further found that the regulation of GDF11 on macrophage polarization through TGFβR1/smad2 pathway. Our results revealed that GDF11 ameliorated SAP and diminished M1 macrophage polarization and facilitated M2 macrophage polarization. The Role of GDF11 in modulating macrophage polarization might be one of the mechanisms by which GDF11 played a protective role in pancreatic tissues during SAP.
Insights
Growth and differentiation factor 11 (GDF11) alleviates severe acute pancreatitis (SAP) by promoting anti-inflammatory M2 macrophages and reducing pro-inflammatory M1 macrophages. This study reveals GDF11
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Severe acute pancreatitis (SAP) is a life-threatening inflammatory condition.
- Macrophages, polarized into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes, are key players in SAP pathogenesis.
- Growth and differentiation factor 11 (GDF11) is known to suppress inflammation, but its role in SAP and macrophage polarization is unclear.
Purpose of the Study:
- To investigate the therapeutic potential of GDF11 in SAP.
- To elucidate the mechanism of GDF11's action on macrophage polarization in SAP.
Main Methods:
- SAP models were established in mice and rats using caerulein and sodium taurocholate, respectively.
- GDF11 treatment effects were assessed via serology, histopathology, and inflammation markers.
- Macrophage polarization was analyzed in vivo and in vitro using cell lines (Raw264.7, THP1).
- RNA/proteome sequencing and pathway analysis identified the TGFβR1/smad2 signaling pathway.
Main Results:
- GDF11 significantly alleviated pancreatic tissue damage in both mouse and rat SAP models.
- GDF11 treatment shifted macrophage polarization towards the M2 phenotype and suppressed the M1 phenotype.
- The protective effects of GDF11 were mediated through the TGFβR1/smad2 signaling pathway.
Conclusions:
- GDF11 demonstrates a protective role in ameliorating SAP.
- GDF11 modulates macrophage polarization, favoring an anti-inflammatory M2 phenotype over a pro-inflammatory M1 phenotype.
- Targeting GDF11 and macrophage polarization presents a potential therapeutic strategy for SAP.
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