Therapeutic Effects of FK506 on IgA Nephropathy Rat

Background/Aims: FK506 is an immunosuppressive drug and a calcineurin inhibitor that has been widely used in kidney disease in recent years. FK506 shows a wide range of biological and pharmaceutical effects; however, the mechanism of its anti- proliferative effect has not been well elucidated. An Ig...

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Published in:Kidney & blood pressure research 2018-01, Vol.42 (6), p.983-998
Main Authors: Linting Wei, Du, Yan, Jia, Lining, Ma, Xiaotao, Chen, Zhao, Lu, Jiamei, Tian, Lifang, Duan, Zhaoyang, Dong, Fengming, Lv, Zhian, Yao, Ganglian, Fu, Rongguo, Wang, Li
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological effects
Bipolar disorder
Calcineurin
Calcineurin inhibitors
Cell growth
Cell proliferation
Drug dosages
Gene expression
Hematuria
IgA nephropathy
Immunoglobulin A
Immunoglobulins
Immunosuppressive agents
Kidney diseases
Kidneys
Kinases
Phosphorylation
Polymerase chain reaction
Proteins
Proteinuria
Renal function
Rodents
Signal transduction
Staining
Studies
Tacrolimus
Transcription
Transient receptor potential proteins
Uric acid
Western blotting
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Summary:Background/Aims: FK506 is an immunosuppressive drug and a calcineurin inhibitor that has been widely used in kidney disease in recent years. FK506 shows a wide range of biological and pharmaceutical effects; however, the mechanism of its anti- proliferative effect has not been well elucidated. An IgA nephropathy (IgAN) model was used to generate a mesangial cell proliferation model. This study aims to examine the effect of FK506 on IgAN rats and the underlying mechanisms. Methods: Hematuria, proteinuria and renal function were measured. To observe the pathological conditions, we performed HE (hematoxylin - eosin) and PAS (periodic acid - schiff) staining. Transcription and protein expression levels were detected by qRT - PCR (quantitative real-time polymerase chain reaction) and Wb (western blotting). The location and semi-quantitative expression levels of TRPCs, CaN (Calcineurin) and α-SMA were examined by IHC (Immunohistochemical staining). Results: We found that FK506 could improve hematuria, proteinuria and renal function, especially in the HF (high-dose FK506) groups. Renal pathological changes were ameliorated in the treatment groups. FK506 could significantly decrease TRPCs, CaN, phosphorylation of ERK1/2 and α-SMA expression. Conclusion: Taken together, these results suggest that the therapeutic effect of FK506 on IgAN might be partially associated with the down-regulated expression of TRPC channels, CaN and phosphorylation of ERK1/2.
ISSN:1420-4096
1423-0143