High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells.
Deposition of collagen IV in proximal tubule cells (PTCs) plays an important role during diabetic nephropathy, but the mechanism underlying excessive production of collagen IV remains poorly understood. In this study, we examined the miRNA profile of HK-2 cells and found that high glucose/TGF-beta1 induced significant down-regulation of miR-29a. We then showed that miR-29a negatively regulated collagen IV by directly targeting the 3'UTRs of col4a1 and col4a2. These results suggest that miR-29a acts as a repressor to fine-tune collagen expression and that the reduction of miR-29a caused by high glucose may increase the risk of excess collagen deposition in PTCs.
Du
Bin
B
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, PR China.
Ma
Li-Ming
LM
Huang
Mian-Bo
MB
Zhou
Hui
H
Huang
Hui-Lin
HL
Shao
Peng
P
Chen
Yue-Qin
YQ
Qu
Liang-Hu
LH
D020413:3' Untranslated Regions / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D020413:3' Untranslated Regions; C547475:COL4A1 protein, human; C502625:COL4A2 protein, human; D024141:Collagen Type IV; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; D005947:Glucose