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Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition.

Hu N, Duan J, Li H, Wang Y, Wang F, Chu J, Sun J, Liu M, Wang C, Lu C, Wen A - PLoS ONE (2016)

Bottom Line: HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group.The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group.Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT

Objective: Renal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs). The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA) can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms.

Methods: Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg) were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1) stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue and HK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot.

Results: HSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P<0.05). HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group. The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group. Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1. Further study revealed that HSYA regulated the TGF-β1/Smads signaling pathway both in kidney tissue and HK-2 cells.

Conclusions: These results suggested that HSYA had a protective effect against fibrosis in renal cells, at least partly, through inhibiting TGF-β1/smad3-mediated Epithelial-mesenchymal transition signaling pathway.

No MeSH data available.


Related in: MedlinePlus

Effect of HSYA on cell proliferation.Cells were incubated for 12h, 24h and 48h in different concentration of HSYA to measure the toxicity (A). The HSYA-treated group stimulated with both recombinant TGF-β1 (5ng/ml) and the different concentrations for three time points (B). Data are expressed as percentage of control group ±SD (n = 3), ##P<0.01compared with control group; *P<0.05 and **P<0.01compared with TGF-β1-treated group.
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pone.0153409.g004: Effect of HSYA on cell proliferation.Cells were incubated for 12h, 24h and 48h in different concentration of HSYA to measure the toxicity (A). The HSYA-treated group stimulated with both recombinant TGF-β1 (5ng/ml) and the different concentrations for three time points (B). Data are expressed as percentage of control group ±SD (n = 3), ##P<0.01compared with control group; *P<0.05 and **P<0.01compared with TGF-β1-treated group.

Mentions: To investigate whether HSYA inhibits TGF-β1-induced EMT in renal tubule epithelial cells, we firstly observed the toxicity of HSYA at different concentrations (Fig 4A).Then HK-2 cells were stimulated by human recombinant TGF-β1 (5ng/ml), and treated with different concentrations of HSYA. Cell proliferation was significantly inhibited by HSYA in a dose-dependent manner, and the phenomenon was more prominent at 200μg/ml after 24 hours. Then 200μg/ml was applied in the following experiment (Fig 4B).


Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition.

Hu N, Duan J, Li H, Wang Y, Wang F, Chu J, Sun J, Liu M, Wang C, Lu C, Wen A - PLoS ONE (2016)

Effect of HSYA on cell proliferation.Cells were incubated for 12h, 24h and 48h in different concentration of HSYA to measure the toxicity (A). The HSYA-treated group stimulated with both recombinant TGF-β1 (5ng/ml) and the different concentrations for three time points (B). Data are expressed as percentage of control group ±SD (n = 3), ##P<0.01compared with control group; *P<0.05 and **P<0.01compared with TGF-β1-treated group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835075&req=5

pone.0153409.g004: Effect of HSYA on cell proliferation.Cells were incubated for 12h, 24h and 48h in different concentration of HSYA to measure the toxicity (A). The HSYA-treated group stimulated with both recombinant TGF-β1 (5ng/ml) and the different concentrations for three time points (B). Data are expressed as percentage of control group ±SD (n = 3), ##P<0.01compared with control group; *P<0.05 and **P<0.01compared with TGF-β1-treated group.
Mentions: To investigate whether HSYA inhibits TGF-β1-induced EMT in renal tubule epithelial cells, we firstly observed the toxicity of HSYA at different concentrations (Fig 4A).Then HK-2 cells were stimulated by human recombinant TGF-β1 (5ng/ml), and treated with different concentrations of HSYA. Cell proliferation was significantly inhibited by HSYA in a dose-dependent manner, and the phenomenon was more prominent at 200μg/ml after 24 hours. Then 200μg/ml was applied in the following experiment (Fig 4B).

Bottom Line: HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group.The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group.Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT

Objective: Renal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs). The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA) can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms.

Methods: Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg) were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1) stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue and HK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot.

Results: HSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P<0.05). HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group. The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group. Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1. Further study revealed that HSYA regulated the TGF-β1/Smads signaling pathway both in kidney tissue and HK-2 cells.

Conclusions: These results suggested that HSYA had a protective effect against fibrosis in renal cells, at least partly, through inhibiting TGF-β1/smad3-mediated Epithelial-mesenchymal transition signaling pathway.

No MeSH data available.


Related in: MedlinePlus