Study on lead-induced activation of rat renal interstitial fibroblasts and the related mechanisms

Abstract Context: Lead is a common industrial toxicant and has been proved to be associated with the kidney damage. Objective: To investigate the effect and mechanism of lead on expression of rat renal interstitial fibroblast activation related protein. Materials and methods: The expression of activation related protein mRNA was measured by real-time PCR in the NRK/49F treated by lead acetate with different concentrations (0, 0.5, 1 and 2 µmol/L). The effects of lead acetate on the level of fibronectin (FN) and signal transduction factors (Smads protein) expression were observed by Western blot. Results: The mRNA expression of activation-related protein increased significantly after the cells were stimulated by lead acetate for 24 h. The lead acetate-treated group could upregulate the p-Smad2, p-Smad3 and FN protein expression compared with the control group. The level of Smad2/3 protein expression did not change in all groups, the expression of SnoN decreased significantly compared with the control group. Discussion and conclusion: Lead acetate could increase the mRNA expression of activation-related factors. It could promote inflammatory reaction induced by TGF-β via Smad signaling pathway. Lead acetate has the effect on inducing the renal fibrosis.

[1]  Q. Wang,et al.  Effects of astragalus injection on the TGFβ/Smad pathway in the kidney in type 2 diabetic mice , 2014, BMC Complementary and Alternative Medicine.

[2]  Y. Tsao,et al.  Notch prevents transforming growth factor-beta-assisted epithelial–mesenchymal transition in cultured limbal progenitor cells through the induction of Smad7 , 2014, Molecular vision.

[3]  Chuzhong Li,et al.  The expression of TGF-β1, Smad3, phospho-Smad3 and Smad7 is correlated with the development and invasion of nonfunctioning pituitary adenomas , 2014, Journal of Translational Medicine.

[4]  F. Strutz,et al.  Renal fibroblasts and myofibroblasts in chronic kidney disease. , 2006, Journal of the American Society of Nephrology : JASN.

[5]  V. Slavkovich,et al.  A Prospective Study of Prenatal and Childhood Lead Exposure and Erythropoietin Production , 2004, Journal of occupational and environmental medicine.

[6]  M. Perazella,et al.  A Review of Chronic Lead Intoxication: An Unrecognized Cause of Chronic Kidney Disease , 2004, The American journal of the medical sciences.

[7]  Sarah B Tegen,et al.  The Transforming Activity of Ski and SnoN Is Dependent on Their Ability to Repress the Activity of Smad Proteins* , 2003, Journal of Biological Chemistry.

[8]  H. Kosmehl,et al.  Fibronectin Splice Variants – Prognostic Markers for the Stage of Renal Interstitial Fibrosis in the Rat , 2002, Nephron.

[9]  J. Murat,et al.  Effect of Chronic Lead Exposure on Kidney Function in Male and Female Rats: Determination of a Lead Exposure Biomarker , 2001, Archives of physiology and biochemistry.

[10]  K. Miyazono,et al.  c-Ski Acts as a Transcriptional Co-repressor in Transforming Growth Factor-β Signaling through Interaction with Smads* , 1999, The Journal of Biological Chemistry.

[11]  K. Luo,et al.  Negative Feedback Regulation of TGF-β Signaling by the SnoN Oncoprotein , 1999 .

[12]  C. Heldin,et al.  Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling , 1997, Nature.

[13]  R. Kalluri,et al.  Early role of Fsp1 in epithelial-mesenchymal transformation. , 1997, American journal of physiology. Renal physiology.

[14]  Y. Okada Volume expansion-sensing outward-rectifier Cl- channel: fresh start to the molecular identity and volume sensor. , 1997, The American journal of physiology.

[15]  F. Strutz,et al.  Identification and characterization of a fibroblast marker: FSP1 , 1995, The Journal of cell biology.

[16]  K. Chia,et al.  Glomerular function of lead-exposed workers. , 1995, Toxicology letters.

[17]  久米 真司 SIRT1 inhibits transforming growth factor β-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation , 2007 .

[18]  N. Kruger,et al.  The bradford method for protein quantitation. , 1988, Methods in molecular biology.