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EphrinB2 Ameliorates Renal Fibrosis by Inhibiting the TGF-β/Smad3 Signaling Pathway and the Inflammation Response
Cheng Yuan1,2, Qiuyuan Zhou3,4, Feng Chen3
1Department of Oncology, Yichang Central People's Hospital and The First College of Clinical Medical Science, China Three Gorges University Yichang, Hubei, 443000, China.
Background:
EphrinB2 is known to play a variety of roles in the pathological process of fibrosis in the heart, skin, and retina, according to current research. However, the role of Ephrin- B2 in renal fibrosis remains to be clarified.
Objective:
We aimed to investigate the role of EphrinB2 in the renal fibrosis model and its underlying mechanisms.
Materials And Methods:
Unilateral ureteral obstruction (UUO) models and TGF-β-treated renal tubular epithelial cells (HK2) were adopted in this study to determine if EphrinB2 could lead to renal fibrosis.
Results:
EphrinB2 was highly expressed in renal tubular cells in UUO mice. Using adeno-associated virus (AAV)-mediated EphrinB2 overexpression, we observed significant improvements in renal function and injury, as well as a marked reduction in fibrosis. For example, EphrinB2 overexpression decreased the expression of fibrosis markers such as Fibronectin and α-SMA by approximately 40%. In vitro, EphrinB2 also significantly reduced extracellular matrix (ECM) deposition and cellular fibrosis under TGF-β stimulation. Mechanistically, EphrinB2 inhibited TGF-β/Smad3 signaling by approximately 40%, and reduced inflammatory markers such as MCP1 and IL-1β by approximately 60% and 35%, respectively.
Conclusions:
This study uncovered a previously unrecognized anti-fibrotic role of EphrinB2 in renal fibrosis, which is achieved through the prevention TGF-β/Smad3 signaling and inflammation response. It seemed that EphrinB2 might be a promising therapeutic target in the treatment of fibrotic diseases and kidney failure.
Insights
EphrinB2 demonstrates an anti-fibrotic effect in kidney fibrosis by inhibiting TGF-β/Smad3 signaling and inflammation. This finding suggests EphrinB2 as a potential therapeutic target for kidney failure and fibrotic diseases.
Area of Science:
- Nephrology
- Molecular Biology
- Pathology
Background:
- EphrinB2 is implicated in fibrosis of the heart, skin, and retina.
- Its role in renal fibrosis is not yet understood.
Purpose of the Study:
- To investigate the role of EphrinB2 in a renal fibrosis model.
- To elucidate the underlying mechanisms of EphrinB2's action in the kidneys.
Main Methods:
- Utilized unilateral ureteral obstruction (UUO) mouse models.
- Employed TGF-β-treated renal tubular epithelial cells (HK2) in vitro.
- Investigated EphrinB2 overexpression using adeno-associated virus (AAV) vectors.
Main Results:
- EphrinB2 was upregulated in renal tubular cells in UUO mice.
- Overexpression of EphrinB2 improved renal function and reduced fibrosis markers (Fibronectin, α-SMA) by ~40%.
- EphrinB2 inhibited TGF-β/Smad3 signaling (~40%) and inflammatory markers (MCP1, IL-1β) by ~60% and ~35%, respectively.
Conclusions:
- EphrinB2 exhibits a novel anti-fibrotic role in renal fibrosis.
- This effect is mediated by the inhibition of TGF-β/Smad3 signaling and inflammation.
- EphrinB2 represents a promising therapeutic target for fibrotic kidney diseases and kidney failure.
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