The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

Ji, Tao; Su, Shulan; Zhu, Yue; Guo, Jianming; Qian, Dawei; Tang, Yuping; Duan, Jin‐Ao

doi:10.1002/ptr.6390

Cited by 15 publications

(11 citation statements)

References 52 publications

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“…All our results indicated that the miR-199a-5p-ZEB1 axis was a downstream target of LUCAT1 and that miR-199a-5p overexpression inhibited the EMT of HG-treated HK-2 cells. ZEB1 is one of the key transcription factors of EMT and plays an important role in promoting the occurrence of this process [25]. Therefore, it is reasonable to hypothesize that LUCAT1 promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p–ZEB1 Axis in Human Renal Tubular Epithelial Cells

Zhang

Wei

Tang

2020

BioMed Research International

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Renal fibrosis, the leading cause of end-stage renal disease and in which epithelial-mesenchymal transition (EMT) plays a central role, has a complex pathogenesis that is not fully understood. Therefore, we investigated the role of the long noncoding RNA LUCAT1 in the EMT of renal tubular epithelial cells under high-glucose (HG) conditions and the underlying mechanism involved. In this study, we established HG and normal glucose groups of HK-2 cells by treating HK-2 cells 30.0 or 5.5 mmol/L glucose, respectively. To investigate the roles of LUCAT1 and miR-199a-5p in HG-induced EMT, we transfected the HG group with negative control small interfering RNA (siRNA), siRNA targeting LUCAT1, negative control microRNA, or an miR-199a-5p mimic. The results of the quantitative reverse transcription PCR indicated that the LUCAT1 level in the HG group was increased, whereas the miR-199a-5p level was decreased. The EMT in the cells was induced by treatment with HG but was weakened by LUCAT1 knockdown or miR-199a-5p overexpression, which both also inhibited the HG-induced phosphorylation of SMAD3. Moreover, LUCAT1 and ZEB1 mRNA comprised the same microRNA response elements of miR-199a-5p. LUCAT1 knockdown had no effect on the miR-199a-5p level but decreased the HG-induced upregulation of ZEB1. In conclusion, HG conditions induced the upregulation of LUCAT1, and LUCAT1 knockdown inhibited the EMT in HG-treated HK-2 cells. LUCAT1 likely promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p.

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Section: Discussionmentioning

confidence: 99%

Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p–ZEB1 Axis in Human Renal Tubular Epithelial Cells

Zhang

Wei

Tang

2020

BioMed Research International

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“…5 Due to the complexities of compound in traditional Chinese medicine, the pathologic process of diabetes can be interfered through the interaction of various mechanisms, which could avoid further damage caused by overuse or underuse of a single target. 22,23 Therefore, YNJ could reduce podocytes injury through multiple signally pathway to avoid high autophagy beyond basal autophagy levels in podocytes exposed to high glucose.…”

Section: Discussionmentioning

confidence: 99%

<p>Yu Nu Compound Regulates Autophagy and Apoptosis Through mTOR in vivo and vitro</p>

He¹,

Guang²,

Zhuang³

et al. 2020

DMSO

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Introduction: Yu Nu compound (YNJ) is a traditional Chinese medicine widely utilized to treat type 2 diabetes possibly through mediating autophagy. Abnormal podocyte autophagy and apoptosis could result in podocyte loss in diabetics nephropathy (DN). The mechanism of Yu Nu compound in DN is still unclear. Therefore, the study aims to investigate the effects of Yu Nu compound and analyze the potential mechanism. Methods: Goto-Kakizaki (GK) rats were administered using YNJ with different doses once a day by gavage for 4 weeks. The renal cortex injury was observed by HE staining and electron microscope. Cell apoptosis of renal cortex was analyzed by TUNNEL staining. The mTOR, autophagy-related proteins and apoptosis-related proteins were detected by Western blot or real-time PCR in vivo and vitro. MPC5 cells were exposed to high glucose (HG, 30mM) for 12h to simulate podocyte injury in DN. MPC5 cells were treated by serum containing YNJ with different dosages. Cell activities and apoptosis were, respectively, detected through Cell Counting Kit-8 (CCK8) assay and flow cytometry. Results: The results showed that the medium dose of YNJ had better effects on decreasing blood glucose and improving renal injury in GK rats, followed by decreasing mTOR levels. The autophagy levels were enhanced in renal cortex, accompanied with the increase of cell apoptosis in vivo. Besides, the proteins regulating autophagy and apoptosis were significantly modulated by YNJ in GK rats. Then, we found that the decreasing endogenous mTOR could reverse the effects of YNJ on podocyte apoptosis and autophagy in vivo. Discussion: The study suggested that YNJ recovered normal autophagy and suppressed apoptosis through regulating mTOR. The maintenance of normal basal autophagic activity possibly based on the effect of YNJ on multiple target was essential for maintaining podocyte function.

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“…The nodes in the network represented medicinal materials, components, targets and pathways, whereas the edges represented medicinal material–component, component–target, and target–pathway interactions. 41–43…”

Section: Methodsmentioning

confidence: 99%

Action Mechanism of Zhuang Medicine Jin-mu Granules Against Chronic Pelvic Inflammatory Disease Explored Using Comprehensive Network Pharmacology and Metabolomics

Wang

et al. 2022

Natural Product Communications

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Zhuang Medicine Jin-mu Granules (ZMJG) are prescriptions derived from the Zhuang nationality, which is the largest minority among 56 ethnic groups in China. They have been widely used in the treatment of chronic pelvic inflammatory disease (CPID) in Guangxi Zhuang Autonomous Region for clearing away heat and toxins, removing dampness and poisoning. CPID is a common gynecological disease of female reproductive organs and surrounding tissues and is characterized by persistent and recurrent symptoms, causing serious physical and psychological damage to the patient. Preliminary research found that ZMJG have beneficial effects on CPID model rats, but the metabolic mechanism underlying their protective effects is unclear. In this study, we used the strategy of combining network pharmacology, pharmacodynamic, and metabolomic approaches to investigate the molecular mechanisms and potential targets of ZMJG for the treatment of CPID. First, a network diagram of “medicinal materials-components-targets-pathways” based on network pharmacology was constructed to obtain a preliminary understanding of the biologically active compounds and related targets of ZMJG and clarify their molecular mechanism in CPID. Subsequently, the in vivo efficacy of ZMJG was verified in a rat model. Furthermore, we analyzed the corresponding metabolomics profile to explore the differentially induced metabolic markers and elucidate the metabolic mechanism by which ZMJG treat CPID. The results show that the therapeutic effect of ZMJG on CPID is mediated through multiple pathways, metabolic pathways, and multi-component multi-target modes, providing a detailed theoretical basis for the development and clinical application of ZMJG and a new research idea for the treatment of CPID in Chinese medicine.

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The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

Cited by 15 publications

References 52 publications

Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p–ZEB1 Axis in Human Renal Tubular Epithelial Cells

Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p–ZEB1 Axis in Human Renal Tubular Epithelial Cells

<p>Yu Nu Compound Regulates Autophagy and Apoptosis Through mTOR in vivo and vitro</p>

Action Mechanism of Zhuang Medicine Jin-mu Granules Against Chronic Pelvic Inflammatory Disease Explored Using Comprehensive Network Pharmacology and Metabolomics

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