Related Experiment Video
Updated: Nov 2, 2025
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
CLEC14A protects against podocyte injury in mice with adriamycin nephropathy
1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China.
Abstract:
Podocyte injury is a major determinant of focal segmental glomerular sclerosis (FSGS) and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance for the treatment of FSGS. CLEC14A is a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family. CLEC14A is found to be expressed in vascular endothelial cells during embryogenesis and is also implicated in tumor angiogenesis. However, the current understanding of the biological functions of CLEC14A in podocyte is very limited. In this study, we found that CLEC14A was expressed in podocyte and protected against podocyte injury in mice with Adriamycin (ADR)-induced FSGS. First, we observed that CLEC14A was downregulated in mice with ADR nephropathy and renal biopsies from individuals with FSGS and other forms of podocytopathies. Moreover, CLEC14A deficiency exacerbated podocyte injury and proteinuria in mice with ADR nephropathy accompanied by enhanced inflammatory cell infiltration and inflammatory responses. In vitro, overexpression of CLEC14A in podocyte had pleiotropic protective actions, including anti-inflammatory and anti-apoptosis effects. Mechanistically, CLEC14A inhibited high-mobility group box 1 protein (HMGB1) release, at least in part by directly binding HMGB1, and suppressed HMGB1-mediated signaling, including NF-κB signaling and early growth response protein 1 (EGR1) signaling. Taken together, our findings provide new insights into the pivotal role of CLEC14A in maintaining podocyte function, indicating that CLEC14A may be an innovative therapeutic target in FSGS.
Insights
The C-type lectin 14A (CLEC14A) protein protects against podocyte injury in focal segmental glomerulosclerosis (FSGS). Downregulation of CLEC14A exacerbates kidney damage, suggesting CLEC14A as a potential therapeutic target for FSGS.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- Podocyte injury is central to focal segmental glomerulosclerosis (FSGS).
- CLEC14A, a transmembrane glycoprotein, has known roles in vascular development and angiogenesis, but its function in podocytes is largely unknown.
- Identifying novel therapeutic targets for podocyte protection is crucial for managing FSGS.
Purpose of the Study:
- To investigate the role of CLEC14A in podocyte injury and its potential as a therapeutic target in FSGS.
- To determine CLEC14A expression levels in FSGS models and human samples.
- To elucidate the protective mechanisms of CLEC14A in podocytes.
Main Methods:
- Analysis of CLEC14A expression in Adriamycin (ADR)-induced FSGS mouse models and human FSGS renal biopsies.
- Assessment of podocyte injury, proteinuria, and inflammatory markers in CLEC14A-deficient mice.
- In vitro studies involving podocyte overexpression of CLEC14A to evaluate its protective effects.
- Investigation of CLEC14A's interaction with high-mobility group box 1 protein (HMGB1) and downstream signaling pathways (NF-κB, EGR1).
Main Results:
- CLEC14A expression was downregulated in ADR-induced FSGS mice and human FSGS samples.
- CLEC14A deficiency aggravated podocyte injury, proteinuria, and inflammation in ADR nephropathy.
- Overexpression of CLEC14A in podocytes demonstrated anti-inflammatory and anti-apoptotic effects.
- CLEC14A inhibited HMGB1 release by binding to HMGB1 and suppressed HMGB1-mediated NF-κB and EGR1 signaling.
Conclusions:
- CLEC14A plays a protective role in maintaining podocyte function and preventing injury.
- CLEC14A downregulation is associated with FSGS progression.
- CLEC14A represents a promising novel therapeutic target for FSGS treatment.
