Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy.

Abstract

BACKGROUND:

IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model.

METHOD:

After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry.

RESULTS:

With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1.

CONCLUSION:

These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

• Authors: Di Liu, Yexin Liu, Guochun Chen, Liyu He, Chengyuan Tang, Chang Wang, Danyi Yang, Huiqiong Li, Zheng Dong, Hong Liu
• Journal: American journal of nephrology (Am J Nephrol) Vol. 45 Issue 4 Pg. 293-300 ( 2017) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 28237991 (Publication Type: Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Ccnd1 protein, rat
• Immunosuppressive Agents
• Cyclin D1
• mTOR protein, rat
• Ribosomal Protein S6 Kinases
• Rps6kb1 protein, rat
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Animals
• Autophagy (drug effects)
• Cell Proliferation (drug effects)
• Cyclin D1 (metabolism)
• Disease Models, Animal
• Glomerulonephritis, IGA (drug therapy, pathology, urine)
• Humans
• Immunohistochemistry
• Immunosuppressive Agents (therapeutic use)
• Mesangial Cells (drug effects, pathology, ultrastructure)
• Microscopy, Electron
• Proteinuria (drug therapy, urine)
• Rats
• Rats, Sprague-Dawley
• Ribosomal Protein S6 Kinases (metabolism)
• Signal Transduction (drug effects)
• Sirolimus (therapeutic use)
• TOR Serine-Threonine Kinases (metabolism)