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Smad3 Signatures in Renal Inflammation and Fibrosis
Wenjing Wu1,2,3,4, Xiaoqin Wang3, Xueqing Yu1
1Guangdong-Hong Kong Joint Laboratory for Immunological and Genetic Kidney Disease, Department of Pathology, and Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China.
Abstract:
Renal inflammation and fibrosis are key pathological features of acute kidney injury (AKI) and chronic kidney disease (CKD). Smad3 is a critical mediator of TGF-β signaling and plays a pathogenic role in both renal inflammation and fibrosis. Smad3 can be activated not only by TGF-β1 but also by many stress molecules including angiotensin II (Ang II), advanced end products (AGEs), and C-reactive protein (CRP) under disease conditions. In addition, Smad3 can interact with other signaling pathways, such as the ERK/p38 MAPK and NF-κB pathways, to mediate renal inflammation and fibrosis. Mechanistically, Smad3 transcriptionally regulates many downstream target genes including microRNAs and long non-coding RNAs to cause cell death, inflammation, and fibrosis. Thus, targeting Smad3 or its downstream genes specifically related to renal inflammation and fibrosis should provide a novel therapeutic strategy to combat kidney diseases.
Insights
Smad3 is a key driver of kidney inflammation and fibrosis, activated by various stress signals. Targeting Smad3 offers a promising therapeutic strategy for combating kidney diseases.
Area of Science:
- Nephrology
- Molecular Biology
- Pathology
Background:
- Renal inflammation and fibrosis are hallmarks of acute kidney injury (AKI) and chronic kidney disease (CKD).
- Smad3 acts as a crucial mediator in transforming growth factor-beta (TGF-β) signaling, contributing to kidney damage.
- Smad3 activation is triggered by TGF-β1 and other stress molecules like angiotensin II (Ang II), advanced glycation end products (AGEs), and C-reactive protein (CRP).
Purpose of the Study:
- To elucidate the role of Smad3 in mediating renal inflammation and fibrosis.
- To explore the interaction of Smad3 with other signaling pathways in kidney disease.
- To identify Smad3 as a potential therapeutic target for kidney diseases.
Main Methods:
- Investigated Smad3 activation by various stress molecules.
- Examined the interaction between Smad3 and signaling pathways like ERK/p38 MAPK and NF-κB.
- Analyzed Smad3's transcriptional regulation of downstream target genes, including microRNAs and long non-coding RNAs.
Main Results:
- Smad3 plays a pathogenic role in renal inflammation and fibrosis.
- Smad3 interacts with ERK/p38 MAPK and NF-κB pathways to promote kidney damage.
- Smad3 regulates downstream genes, leading to cell death, inflammation, and fibrosis.
Conclusions:
- Smad3 is a central mediator in the pathogenesis of kidney inflammation and fibrosis.
- Targeting Smad3 or its downstream effectors presents a novel therapeutic avenue for kidney diseases.
- Understanding Smad3's role provides insights into developing treatments for AKI and CKD.
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