title: Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway.
abstract: 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.
authors.affiliation: Division of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lv
authors.affiliation: Division of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wu
authors.affiliation: Division of Endocrinology, Shenyang No. 8 Hospital, Shenyang, Liaoning 110024, China.
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Division of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Clinical Medicine of Seven-Year Education, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Wang