title: Reduced granulation tissue and wound strength in the absence of α11β1 integrin.
abstract: Previous wound healing studies have failed to define a role for either α1β1 or α2β1 integrin in fibroblast-mediated wound contraction, suggesting the involvement of another collagen receptor in this process. Our previous work demonstrated that the integrin subunit α11 is highly induced during wound healing both at the mRNA and protein level, prompting us to investigate and dissect the role of the integrin α11β1 during this process. Therefore, we used mice with a global ablation of either α2 or α11 or both integrin subunits and investigated the repair of excisional wounds. Analyses of wounds demonstrated that α11β1 deficiency results in reduced granulation tissue formation and impaired wound contraction, independently of the presence of α2β1. Our combined in vivo and in vitro data further demonstrate that dermal fibroblasts lacking α11β1 are unable to efficiently convert to myofibroblasts, resulting in scar tissue with compromised tensile strength. Moreover, we suggest that the reduced stability of the scar is a consequence of poor collagen remodeling in α11(-/-) wounds associated with defective transforming growth factor-β-dependent JNK signaling.
authors: Department of Dermatology, University of Cologne, Cologne, Germany.
authors: Jan-Niklas
authors: JN
authors: Schulz
authors: Department of Biomedicine, Centre for Cancer Biomarkers (CCBIO), Norwegian Centre of Excellence, University of Bergen, Bergen, Norway.
authors: Cédric
authors: C
authors: Zeltz
authors: Department of Biomedicine, Centre for Cancer Biomarkers (CCBIO), Norwegian Centre of Excellence, University of Bergen, Bergen, Norway.
authors: Ida W
authors: IW
authors: Sørensen
authors: Department of Biomedicine, Centre for Cancer Biomarkers (CCBIO), Norwegian Centre of Excellence, University of Bergen, Bergen, Norway.
authors: Malgorzata
authors: M
authors: Barczyk
authors: Department of Biomedicine, Centre for Cancer Biomarkers (CCBIO), Norwegian Centre of Excellence, University of Bergen, Bergen, Norway.
authors: Sergio
authors: S
authors: Carracedo
authors: Department of Dermatology, University of Cologne, Cologne, Germany.
authors: Ralf
authors: R
authors: Hallinger
authors: Institute of Biomechanics and Orthopedics, German Sport University, Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics, University of Cologne, Cologne, Germany.
authors: Anja
authors: A
authors: Niehoff
authors: Department of Dermatology, University of Cologne, Cologne, Germany. Electronic address: beate.eckes@uni-koeln.de.
authors: Beate
authors: B
authors: Eckes
authors: Department of Biomedicine, Centre for Cancer Biomarkers (CCBIO), Norwegian Centre of Excellence, University of Bergen, Bergen, Norway. Electronic address: donald.gullberg@biomed.uib.no.
authors: Donald
authors: D
authors: Gullberg
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology* / Q000503:physiopathology*; D003094:Collagen / Q000502:physiology; D005260:Female; D006097:Granulation Tissue / Q000473:pathology / Q000502:physiology*; D066298:In Vitro Techniques; D016023:Integrins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D058628:Myofibroblasts / Q000473:pathology / Q000502:physiology; D038981:Receptors, Collagen / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013718:Tensile Strength / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016023:Integrins; D038981:Receptors, Collagen; D016212:Transforming Growth Factor beta; C467800:integrin alpha11beta1; D003094:Collagen; D048670:MAP Kinase Kinase 4
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