Lv C.,Liaoning Medical University |
Wu C.,Liaoning Medical University |
Zhou Y.-H.,Shenyang No 8 Hospital |
Shao Y.,Liaoning Medical University |
And 2 more authors.
International Journal of Endocrinology | Year: 2014
The aim of this study was to investigate whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation and extracellular matrix production via mTOR/p70S6K/4E-BP1 signaling. The effect of LA on high glucose-induced cell proliferation, fibronectin (FN), and collagen type I (collagen-I) expression and its mechanisms were examined in cultured rat mesangial cells by methylthiazol tetrazolium (MTT) assay, flow cytometry, ELISA assay, and western blot, respectively. LA at a relatively low concentration (0.25 mmol/L) acted as a growth factor in rat mesangial cells, promoted entry of cell cycle into S phase, extracellular matrix formation, and phosphorylated AKT, mTOR, p70S6K, and 4E-BP1. These effects disappeared when AKT expression was downregulated with PI3K/AKT inhibitor LY294002. Conversely, LA at a higher concentration (1.0 mmol/L) inhibited high glucose-induced rat mesangial cell proliferation, entry of cell cycle into S phase, and extracellular matrix exertion, as well as phosphorylation of mTOR, p70S6K, and 4E-BP1 but enhanced the activity of AMPK. However, these effects disappeared when AMPK activity was inhibited with CaMKK inhibitor STO-609. These results suggest that LA dose-dependently regulates mesangial cell proliferation and matrix protein secretion by mTOR/p70S6K/4E-BP1 signaling pathway under high glucose conditions. © 2014 Chuan Lv et al.
Lv C.,Shenyang University |
Zhou Y.-hong.,Shenyang No 8 Hospital |
Wu C.,Shenyang University |
Shao Y.,Shenyang University |
And 2 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2015
Background: Circulating microRNA 130b has been closely associated with multiple diseases in humans such as cancer, obesity and diabetes mellitus. This study evaluates the correlation between serum miR-130b and the severity of diabetic nephropathy evaluated by measurement of albuminuria. Methods: Three hundred twenty-seven patients with type 2 diabetes mellitus (T2DM) were divided into three groups: normoalbuminuria group [diabetes mellitus, urinary albumin to creatinine ratio (UACR)<30 mg/g, n=137], microalbuminuria group (DN1, UACR 30-300 mg/g, n=122) and macroalbuminuria group (DN2, UACR>300 mg/g, n=68). The levels of serum miR-130b were validated by real-time polymerase chain reaction. Serum transforming growth factor β1 (TGF-β1), hypoxia inducible factor 1α (HIF-1α) and fibronectin were determined by enzyme-linked immunosorbent assay. Results: Compared with control, serum miR-130b levels were significantly decreased in T2DM patients and further decreased in the patients of diabetes mellitus, DN1 and DN2 groups (p<0.001). Furthermore, age-adjusted and sex-adjusted regression analyses showed that decreased level of serum miR-130b, increased levels of glycated haemoglobin (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein (LDL), serum creatinine, blood urea nitrogen (BUN), TGF-β1, HIF-1α and fibronectin were significantly correlated with UACR (p<0.05). In addition, serum miR-130b levels were inversely correlated with HbA1c, HOMA-IR, TG, LDL, BUN, TGF-β1, HIF-1α and FN (p<0.05). Conclusion: Our findings suggest that serum miR-130b may be a new biomarker for the early diagnosis of DN in T2DM. Circulating miR-130b may possibly be involved in the pathological mechanism of DN, such as lipid metabolic disorders, oxidative stress, extracellular matrix deposition and renal fibrosis. © 2015 John Wiley & Sons, Ltd.