[Mechanisms of cordycepin on improving renal interstitial fibrosis via regulating eIF2α/TGF-β/Smad signaling pathway].

Abstract

OBJECTIVE:

To investigate the effects and mechanisms of cordycepin,an effective component of cordyceps militaris, on renal interstitial fibrosis (RIF) and its related eIF2α/TGF-β/Smad signaling pathway.

METHOD:

Firstly, 15 C57BL/6 mice were randomly divided into 3 groups,the control group (Group A), the model group (Group B) and the cordycepin-treated group (Group C). After renal interstitial fibrotic model was successfully established by unilateral ureteral obstruction (UUO), the mice in Group C were intraperitoneally administrated with cordycepin(5 mg x kg(-1) d(-1)) and the ones in Group A and B were administrated with physiological saline for 5 days. At the end of the study, the obstructed kidneys were collected and detected for the pathological changes of RIF, and the mRNA expressions of collagen type I (Col I) and α-smooth muscle actin (α-SMA) in the kidney by Northern blot. Secondly, after renal tubular epithelial (NRK-52E) cells cultured in vitro were exposed to transforming growth factor (TGF) -β with or without cordycepin, the mRNA expressions of Col I and collagen type IV( Col IV) by Northern blot, and the protein expressions of eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α ( p-eIF2α), Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were tested by Western blot.

RESULT:

In vivo, cordycepin alleviated RIF in model mice, including improving fibrotic pathological characteristics and mRNA expressions of Col I and α-SMA. In vitro, cordycepin induced the high expression of p-elF2α, and inhibited the expressions of p-Smad2/3, Col I and Col IV induced by TGF-β in NRK-52E cells.

CONCLUSION:

Cordycepin attenuates RIF in vivo and in vitro, probably by inducing the phosphorylation of eIF2α, suppressing the expression of p-Smad2/3, a key signaling molecule in TGF-β/Smad signaling pathway, and reducing the expressions of collagens and α-SMA in the kidney.

• Authors: Liu-bao Gu, Rong-wen Bian, Yue Tu, Hao Hu, Yi-gang Wan, Wei Sun
• Journal: Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica (Zhongguo Zhong Yao Za Zhi) Vol. 39 Issue 21 Pg. 4096-101 (Nov 2014) ISSN: 1001-5302 [Print] China
• PMID: 25775775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Deoxyadenosines
• Smad Proteins
• Transforming Growth Factor beta
• alpha-smooth muscle actin, mouse
• Protein Serine-Threonine Kinases
• eIF2alpha kinase, mouse
• cordycepin

Topics

• Actins (analysis)
• Animals
• Deoxyadenosines (pharmacology)
• Fibrosis
• Kidney (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Phosphorylation
• Protein Serine-Threonine Kinases (physiology)
• Signal Transduction (drug effects)
• Smad Proteins (physiology)
• Transforming Growth Factor beta (antagonists & inhibitors, physiology)