title: SDF-1α reduces fibronectin expression in rat mesangial cells induced by TGF-β1 and high glucose through PI3K/Akt pathway.
abstract: Stromal cell-derived factor-1 (SDF-1) is a chemokine and plays an important role in cell migration, whereas its role in diabetic nephropathy has not been illustrated distinctly. We hypothesized that SDF-1α may have an effect on extracellular matrix (ECM) accumulations in mesangial cells exposed to transforming growth factor-β1 (TGF-β1) or high glucose in vitro. The exogenous SDF-1α was added into rat mesangial cells incubated with TGF-β1 or high glucose in the medium. The expression of fibronectin (FN) was quantitated by real-time RT-PCR, and the change of Akt and Smad3 measured by western blotting. SDF-1α, its receptor C-X-C chemokine receptor type 4 (CXCR4) and FN mRNA were expressed in rat mesangial cells. Both TGF-β1 and high glucose raised the mRNA expressions of CXCR4 and FN in the cells. SDF-1α inhibited the elevated FN mRNA expression induced by TGF-β1 and high glucose through CXCR4 and PI3K/Akt signaling pathway, as the effect of SDF-1α was reversed by CXCR4 antagonist AMD3100 and PI3K inhibitor LY294002. Correspondingly, TGF-β1 induced Smad3 phosphorylation was suppressed when PI3K/Akt signaling pathway was activated by SDF-1α. Based on these findings, we conclude that SDF-1α ameliorates TGF-β1/high glucose induced ECM accumulations in mesangial cells, which may mediate through PI3K/Akt pathway. This novel mechanism may bring a new insight to our understandings of diabetic nephropathy.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Shao
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Shuai
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China.
authors.forename: Daowen
authors.initials: D
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), No. 1095 Jiefang Road, Wuhan, Hubei Province 430030, People's Republic of China. Electronic address: xfyu188@163.com.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D001596:Benzylamines; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D000080027:Cyclams; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051381:Rats; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D002867:Chromones; D000080027:Cyclams; D005353:Fibronectins; D005947:Glucose; D006571:Heterocyclic Compounds; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019718:Receptors, CXCR4; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C486264:Cxcr4 protein, rat; C497787:Smad3 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C088327:plerixafor