αII-spectrin and βII-spectrin do not affect TGFβ1-induced myofibroblast differentiation.
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 αII- and βII-spectrin are required for the phenotypic properties of adult human dermal (myo)fibroblasts. Knockdown of αII- or βII-spectrin in fibroblasts did not affect cell adhesion, cell size and YAP nuclear/cytosolic localization. We further investigated whether αII- and βII-spectrin play a role in the phenotypical switch from fibroblasts to myofibroblasts under the influence of the pro-fibrotic cytokine TGFβ1. Knockdown of spectrins did not affect myofibroblast formation, nor did we observe changes in the organization of αSMA 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 αII- or βII-spectrin. In fact, fibroblasts stimulated with TGFβ1 demonstrated significantly lower endogenous mRNA levels of αII- and βII-spectrin. Taken together, despite the diverse roles of spectrins in a variety of other cells, αII- and βII-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.
['Piersma|Bram|B|http://orcid.org/0000-0002-8452-3030', 'Wouters|Olaf Y|OY|', 'Bank|Ruud A|RA|']
D048868:Adaptor Proteins, Signal Transducing D002448:Cell Adhesion D002454:Cell Differentiation D002465:Cell Movement D002478:Cells, Cultured D024042:Collagen Type I D006801:Humans D058628:Myofibroblasts D010750:Phosphoproteins D012867:Skin D013049:Spectrin D014157:Transcription Factors D053773:Transforming Growth Factor beta1 D014945:Wound Healing D000091102:YAP-Signaling Proteins
Mechanosensing Fibroblast Spectrin TGFβ1 Physiological stiffness