Cell and molecular mechanisms of keratinocyte function stimulated by insulin during wound healing.
BACKGROUND
Regenerative wound repair is a goal of modern medicine. This is important not only for the local repair but also for its beneficial effect to systemic physiological processes. When wounds become chronic, individuals are susceptible to generalized inflammatory cascades that can affect many organs and even lead to death. Skin is the most commonly injured tissue, and its proper repair is important for reestablishment of its barrier function.


RESULTS
We show here that insulin, when topically applied to skin excision wounds, accelerates re-epithelialization and stimulates "maturation" of the healing tissue. These effects are dependent on the insulin receptor but independent of EGF/EGF-R; PI3K-Akt-Rac1 signaling pathways are critically involved, and healing is alpha3 and LN332-dependent.


CONCLUSIONS
Insulin has great potential for the treatments of chronic wounds in which re-epthelialization is impaired. Understanding of the pathways induced by insulin is important for the development of analog molecules that function strictly in healing. Because of its long history of safe use in humans for decades, this protein may prove to be a powerful therapy without major adverse effects.
Liu
Yan
Y
Burn Department, Ruijin hospital, Shanghai JiaoTong University Medical School, Shanghai, PR China. rjliuyan@yahoo.com.cn
Petreaca
Melissa
M
Yao
Min
M
Martins-Green
Manuela
M
D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D039201:Integrin alpha3beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D007328:Insulin; D039201:Integrin alpha3beta1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D000097794:Kalinin