Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy

Chen, Cheng; Gong, Wenyan; Li, Changzheng; Xiong, Fengxiao; Wang, Shaogui; Huang, Junying; Wang, Yu; Chen, Zhiquan; Chen, Qiuhong; Liu, Peiqing; Lan, Tian; Huang, Heqing

doi:10.18632/oncotarget.20205

Cited by 28 publications

(22 citation statements)

References 54 publications

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“…Furthermore, HG is the most potent stimulus leading to the synthesis of ECM, which results in the deposition of collagen and FN in glomerular cells (23). The present study found that exposure of MCs to HG significantly induced the production of collagen IV and FN, consistent with the results of previous studies (22,23). However, this induction was ameliorated by PC-1 NF treatment.…”

Section: Discussionsupporting

confidence: 94%

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PC‑1 NF suppresses high glucose‑stimulated inflammation and extracellular matrix accumulation in glomerular mesangial cells via the Wnt/β‑catenin signaling

et al. 2019

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Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide with high morbidity and mortality. Glomerular mesangial cell (MC) proliferation, inflammatory cell infiltration and extracellular matrix (ECM) accumulation are the main pathological characteristics of DN. A previous study revealed that polycystin-1 N-terminal fragment (PC-1 NF) fusion protein could inhibit ECM accumulation in a mesangial proliferative glomerulonephritis model. However, the role of PC-1 NF fusion protein in DN remains unknown. The results of the present study indicated that PC-1 NF fusion protein significantly abolished high glucose (HG)-induced glomerular MC viability over three time points measured (24, 48 and 72 h). In addition, PC-1 NF suppressed the levels of monocyte chemotactic peptide-1 and tumor necrosis factor α, as well as the expression of fibronectin and collagen IV, in HG-stimulated MCs. Furthermore, PC-1 NF fusion protein efficiently inhibited the activation of Wnt/β-catenin signaling pathway in HG-stimulated MCs. Taken together, these data indicated that PC-1 NF fusion protein inhibited HG-induced MC proliferation, inflammation, and ECM expression via the modulation of the Wnt signaling pathway. The present study indicated that PC-1 NF fusion protein may be a potential agent in treating DN.

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Section: Discussionsupporting

confidence: 94%

“…FN has been recognized as a major component of ECM. Its overexpression contributes to glomerular basement membrane thickening and ECM accumulation in DN (22). Furthermore, HG is the most potent stimulus leading to the synthesis of ECM, which results in the deposition of collagen and FN in glomerular cells (23).…”

Section: Discussionmentioning

confidence: 99%

PC‑1 NF suppresses high glucose‑stimulated inflammation and extracellular matrix accumulation in glomerular mesangial cells via the Wnt/β‑catenin signaling

et al. 2019

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“…AGEs is a stable covalent compound produced by non-enzymatic glycation of proteins, lipids or nucleic acids in long-term hyperglycemia (22). AGEs can promote intracellular signal transduction and mediate diabetic renal dysfunction (23).…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end products and adipocytokines and oxidative stress in placental tissues of pregnant women with gestational diabetes mellitus

Dong

2019

Exp Ther Med

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Correlation between expression levels of advanced glycation end products (AGEs) and adipocytokines and oxidative stress index malondialdehyde (MDA) in placental tissues of pregnant women with gestational diabetes mellitus (GDM) was investigated. Seventy-two cases of GDM pregnant women who received routine prenatal examination and gave birth in the Department of Obstetrics, Binzhou City Center Hospital from March 2016 to May 2017 were collected as the observation group. Another 80 cases of normal pregnant women who gave birth at the same time were selected as the control group. Enzyme linked immunosorbent assay (ELISA) was used to detect the expression levels of AGEs, visfatin, APN and IL-6 in the lysate of placental tissues. MDA levels were measured by thiobarbituric acid method. Correlation of expression levels of AGEs, visfatin, APN, IL-6 and MDA were analyzed. The expression level of MDA in placental tissues of the observation group was significantly higher than that of the control group (t=16.44, P<0.001). The correlation of expression levels between AGEs, adipocytokines and MDA in placental tissues of the two groups was analyzed, and it was found that the expression levels of AGEs, visfatin and IL-6 in the two groups were positively correlated with MDA. There was a significantly negative correlation between APN and MDA in the two groups. The incidence of cesarean section, neonatal hypoglycemia, fetal distress and macrosomia in the observation group was significantly higher than that in the control group (P<0.05). There was no significant difference in the incidence of membrane rupture and premature birth between the two groups (P>0.05). In conclusion, the expression levels of AGEs, visfatin and IL-6 in placental tissues of GDM pregnant women are positively correlated with MDA. There is a significant negative correlation between APN and MDA, and they play an important role in the pathogenesis of GDM.

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“…diabetic nephropathy (dn) is becoming the most pervasive complication for both types i and ii diabetes, and is also the major cause of end-stage renal disease in the majority of developed and developing countries (1). clinically, dn is characterized by mesangial hypertrophy, mesangial cell (Mc) proliferation, albuminuria, extracellular matrix (ecM) accumulation and kidney fibrosis (2,3). It has been recognized that the glomerular Mcs and ecM accumulation are involved in a variety of biological events (4).…”

Section: Introductionmentioning

confidence: 99%

A novel identified circular RNA, circ_0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR‑101b by targeting TGFβRI

Mou¹,

Chenv²,

Zhou³

et al. 2020

Mol Med Rep

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circular rnas (circrnas) have crucial roles in various diseases; however, the mechanisms of action underlying circrnas in the occurrence and development of diabetic nephropathy (dn) remains largely unknown. The present study investigated the differentially expressed circrnas in the dn mice kidney cortex using circrna sequencing and elucidated the role of circrnas in mesangial cells. it was revealed that 40 circrnas were unconventionally expressed, including 18 upregulated circrnas and 22 downregulated circRNAs. Furthermore, circ_0000491 levels were significantly augmented in both dn mice and high glucose (HG, 30 mM)-induced mouse mesangial cells (MeS13 cells). Knockdown of circ_0000491 significantly suppressed the increase of vimentin, fibronectin and α-smooth muscle actin, as well as collagen type i, iii and iV, whilst reversing the decrease of e-cadherin in HG-induced MeS13 cells. it was further revealed that circrna_0000491 sponged mir-101b and that mir-101b directly targets TGFβri. in addition, the expression levels of mir-101b were negatively associated with the transcriptional level of circrna_0000491 and mir-101b inhibitors reversed the suppression of extracellular matrix (ecM)-associated protein synthesis mediated by knocking-down circrna_0000491. in conclusion, the present study investigated the circrna_0000491/mir-101b/TGFβri axis in ecM accumulation and fibrosis-associated protein expression levels of mesangial cells, which suggested that circRNA_0000491 may be beneficial for the development of an effective therapeutic target for dn.

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Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy

Cited by 28 publications

References 54 publications

PC‑1 NF suppresses high glucose‑stimulated inflammation and extracellular matrix accumulation in glomerular mesangial cells via the Wnt/β‑catenin signaling

PC‑1 NF suppresses high glucose‑stimulated inflammation and extracellular matrix accumulation in glomerular mesangial cells via the Wnt/β‑catenin signaling

Advanced glycation end products and adipocytokines and oxidative stress in placental tissues of pregnant women with gestational diabetes mellitus

A novel identified circular RNA, circ_0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR‑101b by targeting TGFβRI

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