Reg4 regulates pancreatic regeneration following pancreatitis via modulating the Notch signaling
Juanjuan Dai1,2,3, Yan He1,2, Mingjie Jiang2,4
1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Pancreatic regeneration after acute pancreatitis is critical in the normal restoration of pancreatic exocrine function, the inhibition of which can cause severe complications including pancreatic exocrine insufficiency. However, the regulators of pancreatic regeneration and the underlying mechanisms remain uncovered. Here, using the inducible Tet-on system, we found that regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration after pancreatitis. Both acinar-to-ductal metaplasia and the resolution of pancreatitis during regeneration were affected by Reg4 knockdown. Further investigations confirmed that Reg4 exerted its function through regulating Notch activation both in vitro and in vivo. Our study revealed Reg4 as a new regulator and potential therapeutic target for pancreatic regeneration.
Insights
Regenerating family member 4 (Reg4) is crucial for pancreatic regeneration after pancreatitis. Reg4 knockdown impairs acinar-to-ductal metaplasia and resolution by regulating Notch activation, highlighting its therapeutic potential.
Area of Science:
- Gastroenterology and Hepatology
- Cell Biology
- Regenerative Medicine
Background:
- Pancreatic regeneration is vital for restoring exocrine function after acute pancreatitis.
- Failure in regeneration can lead to severe complications like pancreatic exocrine insufficiency.
- The molecular regulators and mechanisms governing pancreatic regeneration are not fully understood.
Purpose of the Study:
- To identify novel regulators of pancreatic regeneration.
- To elucidate the mechanisms underlying Reg4's role in pancreatic regeneration.
- To explore Reg4 as a potential therapeutic target for pancreatitis.
Main Methods:
- Utilized an inducible Tet-on system for gene manipulation.
- Performed Reg4 knockdown in models of acute pancreatitis.
- Assessed acinar-to-ductal metaplasia and pancreatitis resolution.
- Investigated Reg4's effect on Notch signaling pathway activation in vitro and in vivo.
Main Results:
- Regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration.
- Reg4 deficiency affected both acinar-to-ductal metaplasia and the resolution phase of pancreatitis.
- Reg4 was confirmed to regulate Notch activation, a key pathway in regeneration.
- Reg4 plays a critical role in the recovery process following pancreatic injury.
Conclusions:
- Regenerating family member 4 (Reg4) is a newly identified regulator of pancreatic regeneration.
- Reg4 influences pancreatic recovery by modulating Notch signaling.
- Reg4 represents a potential therapeutic target for enhancing pancreatic regeneration and treating pancreatitis.
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