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Updated: May 20, 2026
10:15
Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
Inorganic phosphate stimulates fibronectin expression in renal fibroblasts
Zhonghai Chen1, Dong Chen, Thomas L McCarthy
1Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Summary
Mildly elevated phosphate levels significantly increase fibronectin (FN) production in kidney cells. This process involves specific signaling pathways (ERK1/2, AKT) and transcription factors, contributing to chronic kidney disease (CKD) progression.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Elevated plasma phosphate is linked to chronic kidney disease (CKD) progression.
- Interstitial fibrosis is a key factor in CKD advancement.
Purpose of the Study:
- To investigate how inorganic phosphate influences fibronectin (FN) synthesis in kidney fibroblasts.
- To identify the signaling pathways and transcription factors involved in phosphate-induced FN expression.
Main Methods:
- Utilized a kidney fibroblast cell line (NRK-49F).
- Measured FN abundance and messenger RNA (mRNA) levels.
- Analyzed the roles of ERK1/2, AKT, osterix, NFATc1, and c-Fos.
Main Results:
- Phosphate increased FN abundance and mRNA in a dose-dependent manner.
- ERK1/2 and AKT signaling pathways were crucial for phosphate-dependent FN expression.
- Phosphate stimulated osterix, NFATc1, and c-Fos expression, which mediated FN synthesis.
Conclusions:
- Mildly elevated serum phosphate can induce fibronectin synthesis in kidney fibroblasts.
- This induction is mediated by ERK1/2 and AKT signaling pathways.
- A transcriptional complex involving NFATc1, osterix, and c-Fos regulates fibronectin synthesis.
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