Publication

alpha II-spectrin and beta II-spectrin do not affect TGF beta 1-induced myofibroblast differentiation

Piersma, B., Wouters, O. Y. & Bank, R. A., Oct-2018, In : Cell and Tissue Research. 374, 1, p. 165-175 11 p.

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Mechanosensing of fibroblasts plays a key role in the development of fibrosis. So far, no effective treatments are available to treat this devastating disorder. Spectrins regulate cell morphology and are potential mechanosensors in a variety of non-erythroid cells, but little is known about the role of spectrins in fibroblasts. We investigate whether II- and II-spectrin are required for the phenotypic properties of adult human dermal (myo)fibroblasts. Knockdown of II- or II-spectrin in fibroblasts did not affect cell adhesion, cell size and YAP nuclear/cytosolic localization. We further investigated whether II- and II-spectrin play a role in the phenotypical switch from fibroblasts to myofibroblasts under the influence of the pro-fibrotic cytokine TGF1. Knockdown of spectrins did not affect myofibroblast formation, nor did we observe changes in the organization of SMA stress fibers. Focal adhesion assembly was unaffected by spectrin deficiency, as was collagen type I mRNA expression and protein deposition. Wound closure was unaffected as well, showing that important functional properties of myofibroblasts are unchanged without II- or II-spectrin. In fact, fibroblasts stimulated with TGF1 demonstrated significantly lower endogenous mRNA levels of II- and II-spectrin. Taken together, despite the diverse roles of spectrins in a variety of other cells, II- and II-spectrin do not regulate cell adhesion, cell size and YAP localization in human dermal fibroblasts and are not required for the dermal myofibroblast phenotypical switch.

Original languageEnglish
Pages (from-to)165-175
Number of pages11
JournalCell and Tissue Research
Volume374
Issue number1
Publication statusPublished - Oct-2018

    Keywords

  • Spectrin, Fibroblast, TGF beta 1, Physiological stiffness, Mechanosensing, HIPPO SIGNALING PATHWAY, EMBRYONIC LIVER FODRIN, FIBROBLAST ACTIVATION, SUBSTRATE STIFFNESS, PLASMA-MEMBRANE, CELL CONTACT, SH3 DOMAIN, GROWTH, YAP, FIBROSIS

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