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Reduced granulation tissue and wound strength in the absence of ?11?1 integrin.

ABSTRACT: Previous wound healing studies have failed to define a role for either ?1?1 or ?2?1 integrin in fibroblast-mediated wound contraction, suggesting the involvement of another collagen receptor in this process. Our previous work demonstrated that the integrin subunit ?11 is highly induced during wound healing both at the mRNA and protein level, prompting us to investigate and dissect the role of the integrin ?11?1 during this process. Therefore, we used mice with a global ablation of either ?2 or ?11 or both integrin subunits and investigated the repair of excisional wounds. Analyses of wounds demonstrated that ?11?1 deficiency results in reduced granulation tissue formation and impaired wound contraction, independently of the presence of ?2?1. Our combined in vivo and in vitro data further demonstrate that dermal fibroblasts lacking ?11?1 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 ?11(-/-) wounds associated with defective transforming growth factor-?-dependent JNK signaling.

SUBMITTER: Schulz JN

PROVIDER: S-EPMC4407012 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Reduced granulation tissue and wound strength in the absence of α11β1 integrin.

Schulz Jan-Niklas JN Zeltz Cédric C Sørensen Ida W IW Barczyk Malgorzata M Carracedo Sergio S Hallinger Ralf R Niehoff Anja A Eckes Beate B Gullberg Donald D

The Journal of investigative dermatology 20150129 5

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 α ...[more]

PMID: 25634355

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Project description:BackgroundDelayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury. However, the systematic and detailed evaluation of the scald burn injury, including second-degree deep scald (SDDS) and third-degree scald (TDS), is still unclear. The present study aims to analyze the wound-healing speed, the formation of granulation tissue, and the healing quality after cutaneous damage.MethodsIn order to assess SDDS and TDS, the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice. Furthermore, an excisional wound was administered on the dorsal surface in mice (Cut group). The wound-healing rate was first analyzed at days 0, 3, 5, 7, 15 and 27, with the Cut group as a control. Then, on the full-thickness wounds, hematoxylin and eosin (H&E) staining, Masson staining, Sirius red staining, Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization, the formation of granulation tissue, vascularization, inflammatory infiltration and the healing quality at different time points in the Cut, SDDS and TDS groups.ResultsThe presented data revealed that the wound-healing rate was higher in the Cut group, when compared with the SDDS and TDS groups. H&E staining showed that re-epithelialization, formation of granulation tissue and inflammatory infiltration were greater in the Cut group, when compared with the SDDS and TDS groups. Immunohistochemistry revealed that the number of CD31, vascular endothelial growth factor A, transforming growth factor-β and α-smooth muscle actin reached preferential peak in the Cut group, when compared with other groups. In addition, Masson staining, Sirius red staining, Victoria blue staining, Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III, reticular fibers, failure stress, Young's modulus and failure length in the SDDS group were similar to those in the normal group, suggesting that healing quality was better in the SDDS group, when compared with the Cut and TDS groups.ConclusionOverall, the investigators first administered a comprehensive analysis in the Cut, SDDS and TDS groups through in vivo experiments, which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.

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Reduced granulation tissue and wound strength in the absence of ?11?1 integrin.

Publications

Reduced granulation tissue and wound strength in the absence of α11β1 integrin.

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