Related Experiment Video
Updated: May 19, 2026
Induction of Nephrotic Syndrome in Mice by Retrobulbar Injection of Doxorubicin and Prevention of Volume Retention by Sustained Release Aprotinin
Published on: May 6, 2018
FK506 alleviates proteinuria in rats with adriamycin-induced nephropathy by down-regulating TRPC6 and CaN expression
1Department of Pediatrics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Background:
To investigate the roles of transient receptor potential cation channel 6 (TRPC6) and calcineurin (CaN) in proteinuria pathogenesis and the mechanism of action of the calcineurin inhibitor tacrolimus (FK506) in adriamycin-induced nephropathy.
Methods:
The adriamycin-induced nephropathy rats were established and randomly divided into adriamycin nephropathy (ADR), low-dose FK506 treated (ADR + FK0.5), high-dose FK506 treated (ADR + FK1.0) and Control groups. Twenty-four hour urinary protein and blood biochemistry were measured on weeks 2, 3, 5 and 7, and the distributions and expressions of TRPC6 and CaN in the renal tissue were detected by immunohistochemistry, real-time PCR and Western blot.
Results:
The study showed the 24-hour urinary protein increased significantly in ADR rats compared with Controls whilst for ADR rats hypoalbuminemia, hypercholesterolemia, renal functional lesion and renal pathologic changes appeared. The areas and intensities of TRPC6 and CaN expressed in the glomerulus and tubulointerstitium of ADR rats increased significantly. The expression of TRPC6 mRNA in ADR rats began to increase on the 3rd week and persisted to the 7th week, and CaN mRNA increased throughout the period. Protein expressions of TRPC6 and CaN in ADR rats were significantly higher than those of Controls. FK506 can inhibit CaN activity in the renal tissues and further decrease TRPC6 expression and therefore reduce renal damage and proteinuria in a dose-dependent manner.
Conclusions:
These findings suggested that TRPC6 and CaN were up-regulated on mRNA and protein levels in adriamycin-induced rats. FK506 had a therapeutic effect on the progression of proteinuria and renal damage by down-regulating of TRPC6 and CaN in the renal tissues.
Insights
This study reveals that transient receptor potential cation channel 6 (TRPC6) and calcineurin (CaN) are elevated in adriamycin-induced nephropathy. Tacrolimus (FK506) treatment reduced proteinuria and renal damage by down-regulating TRPC6 and CaN.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Adriamycin-induced nephropathy is a model for studying kidney damage and proteinuria.
- Transient receptor potential cation channel 6 (TRPC6) and calcineurin (CaN) are implicated in proteinuria pathogenesis.
- The mechanism of action of calcineurin inhibitors like tacrolimus (FK506) in this model requires investigation.
Purpose of the Study:
- To investigate the roles of TRPC6 and CaN in adriamycin-induced nephropathy.
- To elucidate the mechanism by which tacrolimus (FK506) exerts its therapeutic effects in this model.
- To determine the impact of FK506 on TRPC6 and CaN expression and activity.
Main Methods:
- Adriamycin-induced nephropathy rat model established and divided into treatment groups (ADR, ADR + low-dose FK506, ADR + high-dose FK506, Control).
- Assessment of 24-hour urinary protein and blood biochemistry at multiple time points (weeks 2, 3, 5, 7).
- Detection of TRPC6 and CaN expression (mRNA and protein) in renal tissue using immunohistochemistry, real-time PCR, and Western blot.
Main Results:
- Adriamycin-induced nephropathy rats exhibited increased urinary protein, hypoalbuminemia, hypercholesterolemia, and renal damage.
- Significant upregulation of TRPC6 and CaN expression (mRNA and protein) observed in glomeruli and tubulointerstitium of ADR rats.
- FK506 treatment demonstrated a dose-dependent inhibition of CaN activity, reduced TRPC6 expression, and ameliorated proteinuria and renal damage.
Conclusions:
- TRPC6 and CaN are upregulated at both mRNA and protein levels in adriamycin-induced nephropathy.
- FK506 exerts a therapeutic effect on proteinuria and renal damage progression.
- The therapeutic mechanism of FK506 involves the downregulation of TRPC6 and CaN in renal tissues.
