title: Spontaneous activity and stretch-induced contractile differentiation are reduced in vascular smooth muscle of miR-143/145 knockout mice.
abstract: OBJECTIVE
  Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non-coding microRNAs are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch-induced differentiation and regulation of L-type calcium channel expression. The aim of this study was to investigate the importance of the smooth muscle-enriched miR-143/145 microRNA cluster for stretch-induced differentiation of the portal vein.
  
  
  METHODS
  Contractile force and depolarization-induced calcium influx were determined in portal veins from wild-type and miR-143/145 knockout mice. Stretch-induced contractile differentiation was investigated by determination of mRNA expression following organ culture for 24 h under longitudinal load by a hanging weight.
  
  
  RESULTS
  In the absence of miR-143/145, stretch-induced mRNA expression of contractile markers in the portal vein was reduced. This was associated with decreased amplitude of spontaneous activity and depolarization-induced contractile and intracellular calcium responses, while contractile responses to 5-HT were largely maintained. We found that these effects correlated with a reduced basal expression of the pore-forming subunit of L-type calcium channels and an increased expression of CaMKIIδ and the transcriptional repressor DREAM.
  
  
  CONCLUSIONS
  Our results suggest that the microRNA-143/145 cluster plays a role in maintaining stretch-induced contractile differentiation and calcium signalling in the portal vein. This may have important implications for the use of these microRNAs as therapeutic targets in vascular disease.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Bhattachariya
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Dahan
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ekman
authors.affiliation: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Boettger
authors.affiliation: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Braun
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Swärd
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hellstrand
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Albinsson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009119:Muscle Contraction / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009924:Organ Culture Techniques; D011169:Portal Vein / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse
keywords: L-type calcium channel; contractility; mechanotransduction; miR-145; microRNA; portal vein