Induction of angiotensin converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility.

Dahan, DianaLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups (författare)

MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that phenotype switching depends on a tissue-specific target of miR-143/145, we found induction of angiotensin converting enzyme in the aorta but not in the bladder where angiotensin converting enzyme was expressed at a low level. Chronic treatment with angiotensin type-1 receptor antagonist restored contractility in miR-143/145-deficient aorta while leaving bladder contractility unaffected. This shows that tissue-specific targets are critical for the effects of miR-143/145 on smooth muscle differentiation and that angiotensin converting enzyme is one such target.

Ekman, MariLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Kärlfysiologi,Cellular Biomechanics,Lund University Research Groups,Vascular Physiology(Swepub:lu)fkem-mpe (författare)
Larsson Callerfelt, Anna-KarinLund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups(Swepub:lu)med-ail (författare)
Turczynska, KarolinaLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)med-ktz (författare)
Boettger, Thomas (författare)
Braun, Thomas (författare)
Swärd, KarlLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Kärlfysiologi,Cellular Biomechanics,Lund University Research Groups,Vascular Physiology(Swepub:lu)mphy-ksw (författare)
Albinsson, SebastianLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-sal (författare)
Cellulär biomekanikForskargrupper vid Lunds universitet (creator_code:org_t)

Ingår i:American Journal of Physiology: Cell Physiology: American Physiological Society307:12, s. 1093-11011522-15630363-6143

Av författaren/redakt...: Dahan, Diana; Ekman, Mari; Larsson Callerfe ...; Turczynska, Karo ...; Boettger, Thomas; Braun, Thomas; visa fler...; Swärd, Karl; Albinsson, Sebas ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Fysiologi

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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