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Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat.

Li X, Shen Y, Lu Y, Yang J - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications.Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy.Knockdown of AR gene expression reversed TGF-β1-induced proliferation of fibroblasts, up-regulation of α-SMA and collagen I expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Wannan Medical College, Wuhu 241002, China.

ABSTRACT
Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-╬▓1, ╬▒-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-╬▓1, AR, ╬▒-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ╬▒-SMA and collagen I induced by TGF-╬▓1, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-╬▓1-induced proliferation of fibroblasts, up-regulation of ╬▒-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

No MeSH data available.


Related in: MedlinePlus

Effect of Epalrestat on TGF-╬▓1-induced expression of ╬▒-SMA and collagen I in cultured pulmonary fibroblasts. (A and B) The expression of ╬▒-SMA mRNA and protein were determined by real-time PCR and Western blot. (C and D) The expression of collagen I mRNA and protein were determined by real-time PCR and Western blot. The values are means┬▒S.E.M. from three independent experiments in vitro. **p<0.01 vs. Control; #p<0.05, ##p<0.01 vs. TGF-╬▓1. EPS, Epalrestat; ╬▒-SMA, ╬▒-smooth muscle actin.
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Figure 5: Effect of Epalrestat on TGF-╬▓1-induced expression of ╬▒-SMA and collagen I in cultured pulmonary fibroblasts. (A and B) The expression of ╬▒-SMA mRNA and protein were determined by real-time PCR and Western blot. (C and D) The expression of collagen I mRNA and protein were determined by real-time PCR and Western blot. The values are means┬▒S.E.M. from three independent experiments in vitro. **p<0.01 vs. Control; #p<0.05, ##p<0.01 vs. TGF-╬▓1. EPS, Epalrestat; ╬▒-SMA, ╬▒-smooth muscle actin.

Mentions: As shown in Fig. 5, exposure of TGF-╬▓1 (5 ng/ml) for 24 h significantly increased ╬▒-SMA and collagen I expression in cultured pulmonary fibroblasts, whereas epalrestat (1, 10, 100 ┬ÁM) obviously inhibited the expression of ╬▒-SMA and collagen I (both mRNA and protein) (p<0.05). Epalrestat (100 ┬ÁM) alone had no effect on ╬▒-SMA and collagen I expression.


Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat.

Li X, Shen Y, Lu Y, Yang J - Korean J. Physiol. Pharmacol. (2015)

Effect of Epalrestat on TGF-╬▓1-induced expression of ╬▒-SMA and collagen I in cultured pulmonary fibroblasts. (A and B) The expression of ╬▒-SMA mRNA and protein were determined by real-time PCR and Western blot. (C and D) The expression of collagen I mRNA and protein were determined by real-time PCR and Western blot. The values are means┬▒S.E.M. from three independent experiments in vitro. **p<0.01 vs. Control; #p<0.05, ##p<0.01 vs. TGF-╬▓1. EPS, Epalrestat; ╬▒-SMA, ╬▒-smooth muscle actin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553399&req=5

Figure 5: Effect of Epalrestat on TGF-╬▓1-induced expression of ╬▒-SMA and collagen I in cultured pulmonary fibroblasts. (A and B) The expression of ╬▒-SMA mRNA and protein were determined by real-time PCR and Western blot. (C and D) The expression of collagen I mRNA and protein were determined by real-time PCR and Western blot. The values are means┬▒S.E.M. from three independent experiments in vitro. **p<0.01 vs. Control; #p<0.05, ##p<0.01 vs. TGF-╬▓1. EPS, Epalrestat; ╬▒-SMA, ╬▒-smooth muscle actin.
Mentions: As shown in Fig. 5, exposure of TGF-╬▓1 (5 ng/ml) for 24 h significantly increased ╬▒-SMA and collagen I expression in cultured pulmonary fibroblasts, whereas epalrestat (1, 10, 100 ┬ÁM) obviously inhibited the expression of ╬▒-SMA and collagen I (both mRNA and protein) (p<0.05). Epalrestat (100 ┬ÁM) alone had no effect on ╬▒-SMA and collagen I expression.

Bottom Line: Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications.Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy.Knockdown of AR gene expression reversed TGF-β1-induced proliferation of fibroblasts, up-regulation of α-SMA and collagen I expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Wannan Medical College, Wuhu 241002, China.

ABSTRACT
Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-╬▓1, ╬▒-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-╬▓1, AR, ╬▒-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ╬▒-SMA and collagen I induced by TGF-╬▓1, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-╬▓1-induced proliferation of fibroblasts, up-regulation of ╬▒-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

No MeSH data available.


Related in: MedlinePlus