UCP2 Upregulates ACSL3 to Enhance Lipid Droplet Release from Acinar Cells and Modulates the Sirt1/Smad3 Pathway to Promote Macrophage‐to‐Myofibroblast Transition in Chronic Pancreatitis Article Swipe
Kunpeng Wang
,
Lilong Zhang
,
Beiying Deng
,
Wanrong Jiang
,
Tianrui Kuang
,
Chen Chen
,
Kailiang Zhao
,
Qiao Shi
,
Jun He
,
Weixing Wang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202412571
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202412571
Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by pancreatic fibrosis and functional decline. Here, we identify macrophage‐to‐myofibroblast transition (MMT) as a novel feature of CP and investigate the role of mitochondrial uncoupling protein 2 (UCP2) in this process. Using mouse models, human pancreatic specimens, and cell lines, we show that UCP2 is markedly upregulated in CP, primarily in acinar cells. UCP2 knockout reduces MMT and alleviates fibrosis, whereas macrophage depletion reverses this protective effect, confirming the central role of MMT. Metabolomic profiling reveals that UCP2 knockout alters lipid metabolism by downregulating acyl‐CoA synthetase long‐chain family member 3 (ACSL3) and reducing lipid droplet (LD) release in acinar cells. Mechanistically, UCP2 upregulation increases silent information regulator 1 (Sirt1) expression, enhances Smad3 phosphorylation and nuclear translocation, and activates transforming growth factor‐β (TGF‐β)/Smad3 signaling to promote macrophage MMT. Macrophage‐specific Sirt1 knockout suppresses both fibrosis and MMT. In conclusion, UCP2 drives CP progression by regulating ACSL3‐mediated LD release in acinar cells and modulating macrophage function through the Sirt1/Smad3 pathway. Targeting UCP2 may represent a promising therapeutic strategy for CP.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/advs.202412571
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202412571
- OA Status
- gold
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413773457
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4413773457Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/advs.202412571Digital Object Identifier
- Title
-
UCP2 Upregulates ACSL3 to Enhance Lipid Droplet Release from Acinar Cells and Modulates the Sirt1/Smad3 Pathway to Promote Macrophage‐to‐Myofibroblast Transition in Chronic PancreatitisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-08-28Full publication date if available
- Authors
-
Kunpeng Wang, Lilong Zhang, Beiying Deng, Wanrong Jiang, Tianrui Kuang, Chen Chen, Kailiang Zhao, Qiao Shi, Jun He, Weixing WangList of authors in order
- Landing page
-
https://doi.org/10.1002/advs.202412571Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202412571Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202412571Direct OA link when available
- Concepts
-
Myofibroblast, Macrophage, Cell biology, Pancreatitis, Lipid droplet, Transition (genetics), Chemistry, Cancer research, Biology, Medicine, Internal medicine, Biochemistry, Fibrosis, In vitro, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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54Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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