ShenKang injection suppresses kidney fibrosis and oxidative stress via transforming growth factor-β/Smad3 signalling pathway <i>in vivo</i> and <i>in vitro</i>

Wu, Xiaoxiao; Guan, Yue; Yan, Jiajia; Liu, Meiyou; Yin, Ying; Duan, Jialin; W, Guo; Hu, Tianxin; Weng, Yan; Xi, Miaomiao; Wen, Aidong

doi:10.1111/jphp.12412

Cited by 27 publications

(30 citation statements)

References 33 publications

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“…One of the affected cytokines is TGF‐β, which has been shown to play a pivotal role in enhancing extracellular matrix synthesis. The enhanced production of collagen, in particular, is associated with the progression of fibrosis . The results of the present study showed that sorbitol levels were higher in the LF tissue from DM (+) patients than in that from DM (−) patients, and that the LF in the DM (+) patients was significantly thicker than that in the DM (−) patients.…”

Section: Discussionsupporting

confidence: 41%

“…The enhanced production of collagen, in particular, is associated with the progression of fibrosis. 20,21 The results of the present study showed that sorbitol levels were higher in the LF tissue from DM (þ) patients than in that from DM (À) patients, and that the LF in the DM (þ) patients was significantly thicker than that in the DM (À) patients. These findings suggest that increased levels of hyperglycemia-induced sorbitol may contribute to LF hypertrophy in DM (þ) LSCS patients.…”

Section: Discussionmentioning

confidence: 48%

“…AR catalyzes the nicotinamide adenosine dinucleotide phosphate (NADPH)‐dependent reduction of glucose to sorbitol. Oxidative‐stress‐mediated tissue damage induces the expression of proinflammatory cytokines and fibrogenic factors such as TGF‐β . To investigate the involvement of AR in the increased sorbitol levels in the LF of DM (+) patients, we examined the effect of the AR inhibitor, epalrestat, on sorbitol levels in NIH3T3 fibroblasts cultured under high glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative-stress-mediated tissue damage induces the expression of proinflammatory cytokines and fibrogenic factors such as TGF-b. 21,24 To investigate the involvement of AR in the increased sorbitol levels in the LF of DM (þ) patients, we examined the effect of the AR inhibitor, epalrestat, on sorbitol levels in NIH3T3 fibroblasts cultured under high glucose conditions. As expected, we found that the sorbitol levels were significantly upregulated in fibroblasts cultured under high glucose conditions, and that the sorbitol levels were dose-dependently reduced by epalrestat treatment.…”

Section: Sorbitol In Diabetic Ligamentumflavummentioning

confidence: 99%

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Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis

et al. 2017

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The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in these patients. Twenty-four diabetic and 20 normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemical methods, and the levels of sorbitol, pro-inflammatory cytokines, and the fibrogenic factor, TGF-β1, in the LF were analyzed. In vitro experiments were performed using NIH3T3 fibroblasts to evaluate the effect of high-glucose conditions and an aldose reductase inhibitor on the cellular production of sorbitol, pro-inflammatory factors, and TGF-β1. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-β1 and of CD68-positive staining than that of the normoglycemic subjects. The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1058-1066, 2017.

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Section: Discussionsupporting

confidence: 41%

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Sorbitol In Diabetic Ligamentumflavummentioning

confidence: 99%

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Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis

et al. 2017

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“…In addition, Klotho was reported to inhibit transforming growth factor‐β1 (TGF‐β1) signalling by directly binding to TGFβ‐RII, this is a vital mechanism for Klotho‐mediated prevention of renal fibrosis 7. TGF‐β1 has been identified as the key profibrogenic cytokine via activating downstream mediators, especially Smad proteins, and finally regulating ECM production 8. Thus, blocking the Klotho/TGF‐β/Smad signalling pathway may be promising for preventing renal fibrosis and preserving renal function.…”

Section: Introductionmentioning

confidence: 99%

Acetyl‐11‐keto‐β‐boswellic acid ameliorates renal interstitial fibrosis via Klotho/TGF‐β/Smad signalling pathway

Liu

Shang

et al. 2018

J Cellular Molecular Medi

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Acetyl‐11‐keto‐β‐boswellic acid (AKBA), an active triterpenoid compound from the extract of Boswellia serrate, has been reported previously in our group to alleviate fibrosis in vascular remodelling. This study aimed to elucidate the in vivo and in vitro efficacy and mechanism of AKBA in renal interstitial fibrosis. The experimental renal fibrosis was produced in C57BL/6 mice via unilateral ureteral obstruction (UUO). Hypoxia‐induced HK‐2 cells were used to imitate the pathological process of renal fibrosis in vitro. Results showed that the treatment of AKBA significantly alleviated UUO‐induced impairment of renal function and improved the renal fibrosis by decreasing the expression of TGF‐β1, α‐SMA, collagen I and collagen IV in UUO kidneys. In hypoxia‐induced HK‐2 cells, AKBA displayed remarkable cell protective effects and anti‐fibrotic properties by increasing the cell viability, decreasing the lactate dehydrogenase (LDH) release and inhibiting fibrotic factor expression. Moreover, in obstructed kidneys and HK‐2 cells, AKBA markedly down‐regulated the expression of TGFβ‐RI, TGFβ‐RII, phosphorylated‐Smad2/3 (p‐Smad2/3) and Smad4 in a dose‐dependent fashion while up‐regulated the expression of Klotho and Smad7 in the same manner. In addition, the effects of AKBA on the Klotho/TGF‐β/Smad signalling were reversed by transfecting with siRNA‐Klotho in HK‐2 cells. In conclusion, our findings provide evidence that AKBA can effectively protect kidney against interstitial fibrosis, and this renoprotective effect involves the Klotho/TGF‐β/Smad signalling pathway. Therefore, AKBA could be considered as a promising candidate drug for renal interstitial fibrosis.

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TGF‐β/Smad and Wnt/β‐catenin signaling pathways are involved in renal fibrosis and its therapies

Ying

Han

Sang

et al. 2020

Clinical & Translational Med

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ShenKang injection suppresses kidney fibrosis and oxidative stress via transforming growth factor-β/Smad3 signalling pathway in vivo and in vitro

Abstract: SKI inhibits renal fibrosis and oxidative stress through downregulation of TGF-β/Smad3 signalling pathway.

Cited by 27 publications

References 33 publications

Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis

Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis

Acetyl‐11‐keto‐β‐boswellic acid ameliorates renal interstitial fibrosis via Klotho/TGF‐β/Smad signalling pathway

TGF‐β/Smad and Wnt/β‐catenin signaling pathways are involved in renal fibrosis and its therapies

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