PI3K/Akt pathway mediates high glucose-induced lipid accumulation in human renal proximal tubular cells via spliced XBP-1.
In the present study, we investigated the effect of X-box-binding protein-1 (XBP-1) splicing on lipogenesis in high glucose-stimulated human renal proximal tubular cell line (HKC). The results revealed that high glucose promoted the splicing of XBP-1, concomitant with up-regulation of lipogenic genes including fatty acid synthase, acetyl-CoA carboxylase, adipocyte differentiation-related protein, and cellular triglyceride. Again, silence of XBP-1 with shRNA vector inhibited high glucose-caused increased lipogenesis. Furthermore, we confirmed that the inhibition of phosphotidyl inositol 3-kinase (PI3K)/Akt pathway with LY294002 or Akt shRNA vector blocked the effect of high glucose on XBP-1 splicing and cellular triglyceride. These above data suggest that spliced XBP-1 mediates high glucose-induced lipid accumulation in HKC cells and PI3K/Akt pathway may be involved in high glucose-caused XBP-1 splicing.
Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
Song
S
Zhao
Lin
L
Zhu
Huijun
H
Duan
Shuxia
S
Liu
Qingjuan
Q
Liu
Wei
W
Liu
Jun
J
Hao
D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D050155:Lipogenesis; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019154:Protein Splicing; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D000071717:X-Box Binding Protein 1
D002867:Chromones; D004268:DNA-Binding Proteins; D054890:Fatty Acid Synthase, Type I; D005947:Glucose; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014280:Triglycerides; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C518729:FASN protein, human