title: PTEN Regulates Renal Extracellular Matrix Deposit via Increased CTGF in Diabetes Mellitus.
abstract: Extracellular matrix accumulation and fibrosis are the features of diabetic nephropathy. PI3K (phosphatidylinositol 3-kinase)/Akt (protein kinase B) signal pathway and its inhibitor PTEN (phosphatase and tensin homolog deleted on chromosome 10) are revealed to modulate renal fibrosis. However, the exact mechanism is still not well known. In the present study we found that compared with normal mice, diabetic mice showed decreased PTEN, increased phospho-Akt (Ser 473), phospho-Akt (Thr 308), CTGF (connective tissue growth factor), α-SMA (α-smooth muscle actin), and matricellular protein in kidney. Knocking down of PTEN caused an increase in phospho-Akt (Ser 473), phospho-Akt (Thr 308), CTGF, secreted fibronectin, and secreted Col 3 in HKC cells (human renal tubular epithelial cells). Again, in vitro experiment revealed 1.89, 2.18, 1.92, 3.06, 2.06-fold increases of phospho-Akt (Ser 473), phospho-Akt (Thr 308), CTGF, secreted fibronectin, and secreted Col 3 in high glucose-stimulated HKC cells in comparison with normal control cells. Furthermore, knocking down of CTGF reversed increased secreted fibronectin and Col 3 in high glucose-treated HKC cells. Moreover, transfection of PTEN expression vector prevented high glucose-caused these changes in HKC cells. Especially, CTGF expression, secretion of fibronectin and Col 3 were, respectively, decreased by 38.81, 53.85, and 39.12%. The treatment of LY294002 inhibited phospho-Akt (Ser 473) and phospho-Akt (Thr 308) expression followed by decreased CTGF, secretory fibronectin and secretory Col 3 in high glucose-treated HKC cells. In the end our study suggests that PTEN regulates renal extracellular matrix production via activated Akt and increased CTGF in diabetes mellitus.
authors.affiliation: Department of Electromyogram, 3rd Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology; D051379:Mice; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002867:Chromones; D055513:Connective Tissue Growth Factor; D004791:Enzyme Inhibitors; D005353:Fibronectins; D005947:Glucose; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: CTGF; DIABETIC NEPHROPATHY; EXTRACELLULAR MATRIX PRODUCTION; HIGH GLUCOSE; PTEN