title: Type 2 Diabetes Monocyte MicroRNA and mRNA Expression: Dyslipidemia Associates with Increased Differentiation-Related Genes but Not Inflammatory Activation.
abstract: OBJECTIVE
  To study the expression pattern of microRNAs and mRNAs related to inflammation in T2D monocytes.
  
  
  METHODS
  A microRNA finding study on monocytes of T2D patients and controls using array profiling was followed by a quantitative Real Time PCR (qPCR) study on monocytes of an Ecuadorian validation cohort testing the top over/under-expressed microRNAs. In addition, monocytes of the validation cohort were tested for 24 inflammation-related mRNAs and 2 microRNAs previously found deregulated in (auto)-inflammatory monocytes.
  
  
  RESULTS
  In the finding study, 142 significantly differentially expressed microRNAs were identified, 15 having the strongest power to discriminate T2D patients from controls (sensitivity 66%, specificity 90%). However, differences in expression of these microRNAs between patients and controls were small. On the basis of >1.4 or <0.6-fold change expression 5 microRNAs were selected for further validation. One microRNA (miR-34c-5p) was validated as significantly over-expressed in T2D monocytes. In addition, we found over expression of 3 mRNAs (CD9, DHRS3 and PTPN7) in the validation cohort. These mRNAs are important for cell morphology, adhesion, shape change, and cell differentiation. Classical inflammatory genes (e.g. TNFAIP3) were only over-expressed in monocytes of patients with normal serum lipids. Remarkably, in dyslipidemia, there was a reduction in the expression of inflammatory genes (e.g. ATF3, DUSP2 and PTGS2).
  
  
  CONCLUSIONS
  The expression profile of microRNAs/mRNAs in monocytes of T2D patients indicates an altered adhesion, differentiation, and shape change potential. Monocyte inflammatory activation was only found in patients with normal serum lipids. Abnormal lipid values coincided with a reduced monocyte inflammatory state.
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands; Department of Immunology, Central University of Ecuador, Quito, Ecuador.
authors.forename: Lucy
authors.initials: L
authors.lastname: Baldeón R
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Weigelt
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: de Wit
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Behiye
authors.initials: B
authors.lastname: Ozcan
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Adri
authors.initials: A
authors.lastname: van Oudenaren
authors.affiliation: Department of Immunology, Central University of Ecuador, Quito, Ecuador.
authors.forename: Fernando
authors.initials: F
authors.lastname: Sempértegui
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.affiliation: Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Grosse
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anton-Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands; Prometeo Program SENESCYT, Central University of Ecuador and Universidad de las Fuerzas Armadas, Quito, Ecuador.
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000235:genetics*; D015331:Cohort Studies; D019295:Computational Biology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D050171:Dyslipidemias / Q000150:complications*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger