PI3K/Akt pathway mediates high glucose-induced lipogenesis and extracellular matrix accumulation in HKC cells through regulation of SREBP-1 and TGF-β1.
Previous studies have shown that high glucose stimulates renal SREBP-1 gene expression and increases renal tubular cells lipid metabolism, however, the mechanisms remain elusive. In the present study we demonstrated that PI3K/Akt pathway was activated in human renal proximal tubular cell line (HKC) exposed to high glucose accompanied with up-regulation of SREBP-1, TGF-β1, lipid droplets deposits and extracellular matrix production. Inhibition of PI3K/Akt pathway by chemical LY294002 or specific short hairpin RNA (shRNA) vector prevented SREBP-1 and TGF-β1 up-regulation, as well as ameliorated HKC cells lipogenesis and extracellular matrix accumulation. These findings indicate that PI3K/Akt pathway potentially mediates high glucose-induced lipogenesis and extracellular matrix accumulation in HKC cells.
Department of Pathology, Hebei Medical University, NO361 Zhongshan East Road, Shijiazhuang, 050017 Hebei, China.
Jun
J
Hao
Shuxia
S
Liu
Song
S
Zhao
Qingjuan
Q
Liu
Xin
X
Lv
Huan
H
Chen
Yunyi
Y
Niu
Huijun
H
Duan
D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D002867:Chromones; D009025:Morpholines; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D053773:Transforming Growth Factor beta1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
J Cell Physiol. 2010 Jul;224(1):59-70
20232305
Kidney Int. 2010 Jul;78(1):48-59
20375990
Cell. 1996 Jun 28;85(7):1037-46
8674110
Cell Cycle. 2009 Oct 15;8(20):3307-10
19838082
Mol Cell Biol. 1995 May;15(5):2582-8
7739539
Cancer Res. 2007 May 1;67(9):4337-45
17483347
Biomaterials. 2009 Oct;30(29):5844-52
19640582
Histochem Cell Biol. 2003 Apr;119(4):267-80
12684813
J Gen Virol. 2010 Jun;91(Pt 6):1388-95
20130133
Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):539-45
15653566
J Agric Food Chem. 2010 Mar 10;58(5):3205-12
20146476
J Am Soc Nephrol. 2010 May;21(5):763-72
20185635
Clin Exp Pharmacol Physiol. 2010 Sep;37(9):e152-7
20590668
J Biol Chem. 2009 Apr 3;284(14):9237-46
19204002
Nat Rev Genet. 2006 Aug;7(8):606-19
16847462
Diabetes. 2005 Jan;54(1):41-50
15616009
Am J Nephrol. 2010;31(4):342-52
20224273
Histochem Cell Biol. 2009 Mar;131(3):327-45
19048273
Am J Physiol Renal Physiol. 2009 Sep;297(3):F822-34
19605547
Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2078-87
18310510
J Biol Chem. 1994 Feb 18;269(7):5241-8
8106507
Kobe J Med Sci. 2009 Nov 24;55(2):E45-52
20847591
Nature. 2004 Nov 11;432(7014):173-8
15538359
J Biol Chem. 1957 May;226(1):497-509
13428781
J Clin Invest. 2006 Sep;116(9):2464-72
16906224
FEBS Lett. 2007 Jun 12;581(14):2715-20
17531980
J Invest Dermatol. 2008 May;128(5):1286-93
17989724
Cancer Res. 2008 Feb 15;68(4):1003-11
18281474
Histochem Cell Biol. 2010 Apr;133(4):467-75
20237793
J Cell Physiol. 2010 May;223(2):397-407
20112290