Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro‐inflammatory factors in vivo and in vitro

Abstract

BACKGROUND AND PURPOSE Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. The present study investigated, in vivo and in vitro, the anti-fibrotic and anti-inflammatory effects, particularly on the epithelial to mesenchymal transition of renal tubular cells, exerted by honokiol, a phytochemical used in traditional medicine, and mechanisms underlying these effects. EXPERIMENTAL APPROACH Anti-fibrotic effects in vivo were assayed in a rat model of renal fibrosis [the unilateral ureteral obstruction (UUO) model]. A rat tubular epithelial cell line (NRK-52E) was stimulated by transforming growth factor-beta 1 (TGF-beta 1) and treated with honokiol to explore possible mechanisms of these anti-fibrotic effects. Gene or protein expression was analysed by Northern or Western blotting. Transcriptional regulation was investigated using luciferase activity driven by a connective tissue growth factor (CTGF) promoter. KEY RESULTS Honokiol slowed development of renal fibrosis both in vivo and in vitro. Honokiol treatment attenuated tubulointerstitial fibrosis and expression of pro-fibrotic factors in the UUO model. Honokiol also decreased expression of the mRNA for the chemokine CCL2 and for the intracellular adhesion molecule-1, as well as accumulation of type I (alpha 1) collagen and fibronectin in UUO kidneys. Phosphorylation of Smad-2/3 induced by TGF-beta 1 and CTGF luciferase activity in renal tubular cells were also inhibited by honokiol. CONCLUSIONS AND IMPLICATIONS Honokiol suppressed expression of pro-fibrotic and pro-inflammatory factors and of extracellular matrix proteins. Honokiol may become a therapeutic agent to prevent renal fibrosis

Protective Role of AMP-Activated Protein Kinase-Evoked Autophagy on an In Vitro Model of Ischemia/Reperfusion-Induced Renal Tubular Cell Injury

“…The signals were visualized by an enhanced chemiluminescence reagents (Millipore Corporation, Billerica, MA, USA) detection system and recorded on X-film. Finally, densitometric analysis was performed using Scion Image software (Scion, Frederick, MD, USA) to quantify protein expression, and the results were normalized to the control group [31,32]. …”

Cyclic stretch-induced TGF-β1 and fibronectin expression is mediated by β1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells

“…Among these, the expressions of fibronectin and TGF-␤1 are upregulated in the UUO model of obstructive nephropathy and may aid the progression to tubulointerstitial fibrosis (12,25,31,34,37,55,66,68). Understanding the regulatory pathways that control their production may be paramount to developing effective therapeutics to treat these diseases.…”

The Effect of Autophagy on Inflammation Cytokines in Renal Ischemia/Reperfusion Injury

“…Hematoxylin and eosin staining was used to detect renal structure damage. In renal I/R, the degree of renal tubule dilation, tubular epithelial cell death, and cast formation was used as standard for determining histological score (0, no change; 1, change affecting less than 25 % of the field; 2, change affecting 25-50 % of the field; 3, change affecting 50-75 % of the field; 4, change affecting more than 75 % of the field) [27,28]. Scores of the 20 sections were averaged to represent a score for each rat.…”