Function of Integrins in Wound Repair

The process of wound healing is the body’s primary mechanism to restore tissue integrity upon injury. If wound healing does not occur properly, chronic disruption of the skin’s protective barrier function may lead to severe physiologic, immunologic, and metabolic derangements. Our research team has for years focused on expanding our knowledge of cell biology of reepithelialization and integrins with special emphasis on oral and epidermal wound healing (reviewed in Hakkinen et al., 2000; Larjava et al., 2002). The goal of the projects listed below is to further that knowledge that will help us to design molecular precision tools aiming at improved healing of chronic wounds, reduction of scarring and regeneration of oro-facial tissues.


  1. Role of epithelial integrins in wound healing
  2. Epithelial regulation of inflammation, granulation tissue formation and scarring
  3. Gene expression during scarless wound healing
  4. Cell signaling in transition of stationary to migratory keratinocyte

During reepithelialization the expression of extracellular matrix receptors, (integrins) is changed. We have reported that the expression of avß6 integrin is linked to the fusion of the epithelium and initiation of granulation tissue formation (Larjava et al., 1993; Haapasalmi et al., 1996; Clark et al, 1996). To investigate the role of avß6 integrin in the context of wound healing, we have created a transgenic mouse with targeted overexpression of human ß6 integrin. Some of these mice develop extensive scarring and/or development of open chronic wounds. Consistent with these findings, avß6 integrin is strongly expressed in chronic human wounds (e.g. diabetic ulcers). Our research team is focusing to find out the mechanisms of avß6 integrin function during normal and aberrant wound healing.

Alterations in wound repair, such as non-healing wounds and fibroproliferative disorders (hypertrophic scarring and keloids) are serious pathologic disorders that compromise skin biomechanical properties, resulting in tissue dysfunction. Interestingly, even normal wound healing process in skin produces scars that can cause not only cosmetic concerns but also lack of reduced function while in oral mucosal tissue wound healing results in minimal or no scarring. Scar-free healing of oral mucosa has been explained by the moist environment, growth factors, cytokines in saliva, and by the unique cell types present in the tissue itself (Hakkinen et al., 2000). There is, however, no detail information describing the differences in gene expression in normal healing of oral mucosa compared to skin or fibroproliferative disorders. Using cDNA microarrays we will analyze the expression of chemokines/cytokines and growth factors during scarless oral wound healing and compare the results to epidermal and aberrant wound healing. This information will be used to analyze target gene expression and function at molecular, cellular and tissue level.

During reepithelialization, keratinocytes migrate from the wound edge into the fibronectin-rich wound provisional matrix. During this process, they form long cellular extensions called lamellipodia, which are necessary for the migratory phenotype (Larjava et al., 1996). The exact mechanism of lamellipodia formation in keratinocytes is unclear. Our laboratory has recently discovered that a signaling molecule GSK-3 plays a critical role in lamellipodia formation and migration of keratinocytes in a process that is driven by HB-EGF. We will continue dissecting the molecular pathways regulating keratinocyte migration during wound healing.


Post Docs

Graduate Students

  • Ameneh Eslami
  • Yangshuang Xie
  • Farzin Ghannad
  • Sarah Johnston
  • Daniela Nica

Visiting Scientists and Research Associates

  • Leeni Koivisto
  • Guoqiao Jiang

Laboratory Technicians

  • Cristian Sperantia