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Updated: Jan 7, 2026
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Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
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Matrix Gla Protein Expression in Pericytes and Myofibroblasts Contributes to Renal Fibrosis
Kyoungmi Bak1, Hyunyun Kim2, Jocelyn S Garland3
1Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada; Shriners Hospital for Children Canada, Montreal, Quebec, Canada.
The American Journal of Pathology
|January 1, 2026
Summary
Matrix Gla protein (MGP) produced by kidney myofibroblasts drives renal fibrosis progression in chronic kidney disease (CKD). Reducing MGP limits fibrosis, suggesting MGP as a therapeutic target for kidney disease.
Area of Science:
- Nephrology
- Pathology
- Molecular Biology
Background:
- Renal fibrosis is a key driver of chronic kidney disease (CKD) progression and poor kidney outcomes.
- Increased serum matrix Gla protein (MGP) is observed in CKD patients, but its role in fibrosis is unclear.
- MGP is a known inhibitor of soft tissue calcification.
Purpose of the Study:
- To investigate the role of MGP in the onset and progression of renal fibrosis.
- To identify the cellular sources of MGP in the kidney during injury.
- To determine if MGP exacerbates kidney fibrosis.
Main Methods:
- Utilized Cre-reporter and knock-in mouse models to track MGP production.
- Administered folic acid (FA) to induce kidney injury in wild-type and MGP-deficient (Mgp-/-) mice.
- Restored MGP expression in myofibroblasts of Mgp-/- mice to assess its impact on fibrosis.
Main Results:
- Pericytes and kidney myofibroblasts were identified as primary MGP sources.
- Mgp-/- mice exhibited significantly reduced renal fibrosis after FA injury compared to controls.
- Restoring MGP in myofibroblasts of Mgp-/- mice reinstated severe renal fibrosis.
Conclusions:
- MGP produced by kidney myofibroblasts exacerbates renal fibrosis in an FA-induced injury model.
- MGP plays a critical role in the pathogenesis of kidney fibrosis.
- Targeting MGP may offer a therapeutic strategy for mitigating CKD progression.
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