Sitagliptin ameliorates high glucose-induced cell proliferation and expression of the extracellular matrix in glomerular mesangial cells

Zhang, Guan‐Ying; Wang, Dongdong; Cao, Zheng; Tong, Wei; Liu, Chen‐Xu; Wei, Qi

doi:10.3892/etm.2017.5002

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…Control HMCs stimulated by the HG-Exos showed increased AGT and renin contents, indicating that the cargo of HG-Exos was efficiently delivered to control cells, and contributed to increase RAS components in unstimulated target cells. As a phenotype response, it was observed a overproduction of fibronectin in HMC exposed to HG-Exos, an cell proliferation increase in target cells, and a similar effect was observed in whole HMCs stimulated with HG 45,46 .…”

Section: Discussionsupporting

confidence: 53%

Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication

Novaes

Borges

Maquigussa

et al. 2019

Sci Rep

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Mesangial cells stimulated with high glucose (HG) exhibit increased intracellular angiotensin II (AngII) synthesis that is correlated with the upregulation of AngII target genes, such as profibrotic cytokines. The intracrine effects of AngII can be mediated by several molecules transferred to other cells via exosomes (Exos), which play a key role in cellular communication under many physiological and pathological conditions. The aim of this study was to investigate the effects of exosomes derived from HG-stimulated human mesangial cells (HG-HMCs) on normal unstimulated HMCs. Exosomes from HMCs (C-Exos) and HG-HMCs (HG-Exos) were obtained from cell culture supernatants. HMCs were incubated with C-Exos or HG-Exos. HG stimulus induced a change in the amount but not the size of Exos. Both C-Exos and HG-Exos contained angiotensinogen and renin, but no angiotensin converting enzyme was detected. Compared with HMCs treated with C-Exos, HMCs treated with HG-Exos presented higher levels of fibronectin, angiotensinogen, renin, AT 1 and AT 2 receptors, indicating that HG-Exos modified the function of normal HMCs. These results suggest that the intercellular communication through Exos may have pathophysiological implications in the diabetic kidney.

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Section: Discussionsupporting

confidence: 53%

Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication

Novaes

Borges

Maquigussa

et al. 2019

Sci Rep

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“…ECM accumulation results in mesangial expansion, tubulointerstitial fibrosis and irreversible deterioration of renal function (26–29). The epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the underlying mechanisms of renal fibrosis, and encompasses a range of events whereby epithelial cells no longer exhibit certain epithelial traits, including E-cadherin expression.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics analysis of sirolimus treatment in lupus nephritis

Wang

Chen

et al. 2019

Mol Med Report

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lupus nephritis (ln) is one of the principal causes of mortality and disability in patients with systemic lupus erythematosus. Sirolimus has been used to treat patients with ln; however, the effects and mechanism of sirolimus in these patients remains unclear. The present study aimed to elucidate the therapeutic effects and mechanisms of sirolimus in ln mice using low, medium and high doses of sirolimus (0.1, 0.3 and 1 mg/kg, respectively). The survival probability and kidney index were calculated, and renal fibrosis was determined using Masson's Trichrome staining. The expression levels of e-cadherin, α-smooth muscle actin (α-SMa) and vimentin were assessed via immunofluorescence analysis. Transcriptome analysis of control and sirolimus-treated ln mice was performed using rna-sequencing, differentially expressed gene (deG) identification and annotation, and Gene ontology (Go) functional and Kyoto encyclopedia of Genes and Genomes (KeGG) pathway enrichment. The results suggested that a medium dose of sirolimus alleviated renal fibrosis and increased the survival rates of mice with LN (P<0.05). Furthermore, transcriptome analysis revealed 334 deGs associated with ln, 176 of which were upregulated and 158 were downregulated. Following Go functional enrichment, 'biological process', 'molecular function' and 'cellular component' terms were identified. a total of 10 KeGG pathways were enriched, with 'cytokine-cytokine receptor interaction' and 'interleukin-17 signaling pathway' being significantly enriched (P<0.05). To the best of our knowledge, the present study is the first to conduct transcriptome analysis of ln mice treated with sirolimus, and demonstrated that a dose of 0.3 mg/kg exerted the greatest therapeutic effects.

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“…However, little progress has been made in the treatment of patients with DN (33). Although certain novel drugs, including dipeptidyl peptidase 4 inhibitors (34-36), sodium glucose cotransporter 2 inhibitors (37,38) and glucagon-like peptide 1 agonists (39), can help patients presenting with early-stage DN by tightly controlling blood glucose level, it remains largely unknown whether these drugs can ameliorate EMT of renal tubular cells, which also occurs in DN.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells

et al. 2018

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Astragaloside IV (AST) is the major active saponin in Astragalus membranaceus and, reportedly, has a variety of pharmacological activities. However, the potential of AST to ameliorate high glucose-mediated renal tubular epithelial-mesenchymal transition (EMT) remains undetermined. The aim of the present research was to explore the effect and mechanism of AST in EMT of renal tubular epithelial cells, as an underlying mechanism of renal fibrosis and a vital feature involved in diabetic nephropathy. The effect of AST on the EMT of renal tubular epithelial cells (HK-2) stimulated by high glucose was investigated and it was attempted to elucidate the potential underlying mechanism. The expression of E-cadherin and α-smooth muscle actin were determined by western blotting and immunofluorescence assays. The expression of the mammalian target of rapamycin complex 1 (mTORC1)/ ribosomal protein S6 kinase β-1 (p70S6K) signaling pathway and protein levels of four transcriptional factors (snail, slug, twist and zinc finger E-box-binding homeobox 1) were also determined by western blotting. Additionally, extracellular matrix components, including fibronectin (FN) and collagen type IV (Col IV) were detected by ELISA. The results suggested that the EMT of HK-2 cells and the mTORC1/p70S6K pathway were activated by high glucose. The expression of snail and twist in HK-2 cells was elevated by high glucose. Furthermore, extracellular matrix components, FN and Col IV, were increased in HK-2 cells cultured with high glucose. In turn, treatment with AST reduced EMT features in HK-2 cells, inhibited mTORC1/p70S6K pathway activation, downregulated expression of snail and twist, and reduced secretion of FN and Col IV. In summary, the findings suggested that AST ameliorates high glucose-mediated renal tubular EMT by blocking the mTORC1/p70S6K signaling pathway in HK-2 cells.

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Sitagliptin ameliorates high glucose-induced cell proliferation and expression of the extracellular matrix in glomerular mesangial cells

Cited by 12 publications

References 29 publications

Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication

Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication

Transcriptomics analysis of sirolimus treatment in lupus nephritis

Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells

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