Related Experiment Video
Updated: Jun 16, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
A comprehensive approach to elucidating the pathophysiology of kidney fibrosis based on extracellular vesicle
Yaerim Kim1, Kyuhyeon Kim2, Hong-Beom Park2
1Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
Introduction:
Transglutaminase 2 (TG2) plays a profibrotic role in chronic kidney disease (CKD), but its role in the exosomal proteome remains unexplored. Here, we aimed to evaluate biological processes specifically involved in CKD progression through exosomal proteomic profiling following TG2 inhibition.
Materials And Methods:
Human proximal tubular epithelial cells (hPTECs) were treated with recombinant transforming growth factor-β (rTGF-β) to induce fibrosis and cysteamine to inhibit TG2. A unilateral ureteral obstruction (UUO) mouse model was used for in vivo validation. EVs were isolated and analyzed using LC-MS/MS analysis. Bioinformatics tools, including enrichGO and STRING, were used to identify key biological pathways and protein interactions. Findings were validated in the UUO mouse model.
Results:
TG2 inhibition attenuated the expression of fibrosis- and inflammation-associated proteins in hPTECs and fibroblasts. EV proteomic analysis revealed distinct protein expression patterns following rTGF-β treatment and TG2 inhibition. Altered proteins were primarily extracellular matrix components such as connective tissue growth factor, IGF-binding protein, laminin, plasminogen activator inhibitor, periostin, and collagen.
Conclusions:
TG2 inhibition modulated EV-associated proteins involved in fibrosis and inflammation, highlighting its therapeutic potential in CKD. Identifying reversible fibrosis-related factors may provide new targets for CKD treatment.
Insights
Transglutaminase 2 (TG2) inhibition reduces fibrosis and inflammation markers in chronic kidney disease (CKD) by altering exosomal proteins. This suggests TG2 is a potential therapeutic target for CKD progression.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Transglutaminase 2 (TG2) is implicated in fibrosis in chronic kidney disease (CKD).
- The role of TG2 in the exosomal proteome during CKD progression is not well understood.
- Exosomes play crucial roles in intercellular communication and disease pathogenesis.
Purpose of the Study:
- To investigate the role of TG2 in the exosomal proteome of CKD.
- To identify biological processes involved in CKD progression through exosomal proteomic profiling after TG2 inhibition.
- To evaluate the therapeutic potential of TG2 inhibition in CKD.
Main Methods:
- Human proximal tubular epithelial cells (hPTECs) were induced to fibrosis using recombinant transforming growth factor-β (rTGF-β) and treated with cysteamine to inhibit TG2.
- A unilateral ureteral obstruction (UUO) mouse model was used for in vivo studies.
- Extracellular vesicles (EVs) were isolated and analyzed using LC-MS/MS, followed by bioinformatics analysis (enrichGO, STRING).
Main Results:
- TG2 inhibition decreased fibrosis- and inflammation-associated proteins in hPTECs and fibroblasts.
- Exosomal proteomic analysis revealed distinct protein expression patterns following rTGF-β treatment and TG2 inhibition.
- Key altered exosomal proteins included extracellular matrix components like connective tissue growth factor, IGF-binding protein, laminin, plasminogen activator inhibitor, periostin, and collagen.
Conclusions:
- TG2 inhibition modulates EV-associated proteins implicated in fibrosis and inflammation.
- These findings highlight the therapeutic potential of targeting TG2 for CKD.
- Identifying reversible fibrosis-related factors offers new therapeutic targets for CKD treatment.
