[Effect of kurarinone on renal tubular epithelial cell-mesenchyma trans-differentiation in rats with renal interstitial fibrosis].

Abstract

OBJECTIVE:

To study the effect of Kurarinone on renal tubular epithelial cell-mesenchyma (ECM) trans-differentiation in rats with renal interstitial fibrosis and to explore its possible mechanisms.

METHODS:

The rat model of renal interstitial fibrosis was established by unilateral ureteral obstruction (UUO). Sprague-Dawley male rats were randomly divided into 3 groups, the sham-operated group, the UUO group and the Kurarinone treated group (KTG). Rats in the KTG were intraperitoneally injected with Kurarinone 100 mg/kg daily after modeling. Five rats of each group were killed respectively at day 7, 14 and 21 after UUO. The serum levels of blood urea nitrogen (BUN), serum creatinine (SCr), total protein (TP) and albumin (ALB), 24-h urinary protein excretion in rats were measured. Pathological changes of renal tissue were observed by PAS and Masson stain. The expression of transforming growth factor beta1 (TGF-beta1), Smad3, alpha-smooth muscle actin (alpha-SMA) and collagen I (Col I) in kidney were determined with immunohistochemistry. And the expressions of TGF-beta1 and alpha-SMA mRNA in renal tissue were determined using reverse transcription polymerase chain reaction (RT-PCR).

RESULTS:

The expression of TGF-beta1, Smad3, alpha-SMA and Col I in the KTG was significantly decreased as compared with that in the UUO group respectively, and the degree of tubular damage and renal interstitial fibrosis was also ameliorated more obviously in the KTG. The TGF-beta1 and alpha-SMA mRNA expressions in KTG were significantly lower than those in the UUO group determined at the corresponding time points (P < 0.05).

CONCLUSION:

Kurarinone could down-regulate the expression of TGF-beta1 and Col I, inhibit EC-M trans-differentiation, suppress the activation and proliferation of myofibroblast. The probable pathway may be by way of down-regulating Smad3 expression to interfere its induction on intercellular signal transduction and consequently ameliorate renal interstitial fibrosis.

• Authors: Hong-Yu Gao, Xiao-Feng He, Ju-Fang Shao
• Journal: Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine (Zhongguo Zhong Xi Yi Jie He Za Zhi) Vol. 27 Issue 6 Pg. 535-9 (Jun 2007) ISSN: 1003-5370 [Print] China
• PMID: 17633368 (Publication Type: English Abstract, Journal Article)

Chemical References

• Collagen Type I
• Flavonoids
• RNA, Messenger
• Transforming Growth Factor beta1
• kurarinone

Topics

• Animals
• Cell Transdifferentiation (drug effects)
• Collagen Type I (biosynthesis, genetics)
• Epithelial Cells (drug effects, metabolism, pathology)
• Fibrosis
• Flavonoids (pharmacology)
• Immunohistochemistry
• Kidney (drug effects, metabolism, pathology)
• Kidney Tubules (drug effects, metabolism, pathology)
• Male
• Mesoderm (drug effects, metabolism, pathology)
• Nephritis, Interstitial (physiopathology)
• RNA, Messenger (biosynthesis, genetics)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta1 (biosynthesis, genetics)