Connexins 26, 30, and 43: Differences Among Spontaneous, Chronic, and Accelerated Human Wound Healing

Brandner, Johanna M.; Houdek, Pia; Hüsing, Birgit; Kaiser, Colette; Moll, Ingrid

doi:10.1111/j.0022-202x.2004.22529.x

Cited by 127 publications

(155 citation statements)

References 48 publications

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…Primers amp l i f y i n g M M P -2 ( H s 0 0 2 3 4 4 2 2 _ m1), TIMP-1 (Hs00171558_m1), TIMP-2 (Hs00234278_m1), IL-1␤ (Hs00174097_m1), TNF-␣ (Hs00174128_ m1), Cx26 (Hs00269615_s1), Cx43 (Hs007748445_s1), and GAPDH (4310884E) were purchased from Applied Biosystems (Weiterstadt, Germany). Rabbit polyclonal antibodies directed to Cx43 (71-0700) were purchased from Zymed Laboratories (San Francisco, CA), and polyclonal antibodies directed against Cx26 were produced as described (10).…”

Section: Primers and Antibodiesmentioning

confidence: 99%

“…Cell culture Keratinocytes were cultured as described (10). Briefly, skin samples were trypsinized overnight at 4°C and then placed in keratinocyte basic medium supplemented with epidermal growth factor, bovine pituitary extract, insulin, hydrocortisone, and glutamine.…”

Section: Primers and Antibodiesmentioning

confidence: 99%

“…Chronic wounds, including chronic foot ulceration, are characterized by a disturbed relation of proinflammatory cytokines (TNF-␣ and IL-1␤), an elevated concentration of MMPs, and altered expression of connexins (2,10,22,23).…”

Section: -Expression (⌬Ct) Of Mmp-1 Mmp-2 Il-1␤ Tnf-␣ Cx26 and Cmentioning

confidence: 99%

“…Transgenic mice deficient for Cx43 in the epidermis as well as mice treated with Cx43 antisense gel exhibit accelerated wound healing (11,12). In chronic wounds, Cx43 is present at the wound margins (10). Recent results suggest an involvement of Cx43 downregulation in migration and proliferation of keratinocytes and fibroblasts as well as in inflammatory response (13).…”

mentioning

confidence: 99%

“…Recent results suggest an involvement of Cx43 downregulation in migration and proliferation of keratinocytes and fibroblasts as well as in inflammatory response (13). Cx26 protein expression is induced in the course of wound healing (10).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Expression of Matrix Metalloproteinases, Cytokines, and Connexins in Diabetic and Nondiabetic Human Keratinocytes Before and After Transplantation Into an Ex Vivo Wound-Healing Model

et al. 2008

Self Cite

View full text Add to dashboard Cite

OBJECTIVE -Wound healing is known to require a well-organized balance of numerous factors, e.g., cytokines, matrix metalloproteinases (MMPs), and their inhibitors, as well as direct cell-cell communication (connexins). Disruption of this balance may lead to the formation of chronic wounds such as diabetic foot ulcers. The transplantation of autologous keratinocytes is a promising therapy for diabetic foot ulcers; however, little is known about their characteristics on a molecular level. Therefore, we intended to characterize transplanted keratinocytes from diabetic and nondiabetic origin before and after transplantation.RESEARCH DESIGN AND METHODS -We isolated human keratinocytes from diabetic and nondiabetic origins and transplanted them into an ex vivo wound healing model. To characterize the keratinocytes, we investigated mRNA expression of MMP-1, MMP-2, and MMP-9; tissue inhibitor of MMP (TIMP)-1 and TIMP-2; interleukin (IL)-1␤, tumor necrosis factor (TNF)-␣; Cx26 (connexin 26) and Cx43; and, for connexins, immunolocalization.RESULTS -We found no significantly increased expression of the molecules investigated in cultured keratinocytes from diabetic compared with nondiabetic origin, even though there were significant differences for MMP-2, IL-1␤, and TNF-␣ in skin biopsies. Expression of IL-1␤ was significantly lower in keratinocytes from diabetic origin. In the course of wound healing, differences in the dynamics of expression of MMP-1, IL-1␤, and Cx43 were observed.CONCLUSIONS -Our results suggest that keratinocytes from diabetic origin are as capable for transplantation into chronic wounds as keratinocytes from healthy origin at the starting point of therapy. However, differences in expression dynamics later on might reflect the systemic influence of diabetes resulting in a memory of the transplanted keratinocytes. Diabetes Care 31:114-120, 2008D iabetic foot syndrome represents a major complication of diabetes causing considerable mortality and substantial lower-limb amputation rates of about 44,000 per year in Germany (1).To comprehend the microenvironment of acute and chronic wounds, the pathophysiology of impaired wound healing has been increasingly investigated. Elevated levels of matrix metalloproteinases (MMPs) and reduced levels of their endogenous tissue inhibitors (tissue inhibitors of MMP [TIMPs]) have been shown in chronic wounds, including diabetic foot lesions, and can result in excessive proteolysis of tissue, as well as of growth factors and their receptors (2-4). MMPs are responsible for controlled degradation of the extracellular matrix as well as migration in normal wound healing. They also affect angiogenesis and remodeling of the dermis. MMPs are produced by several types of cells including fibroblasts, keratinocytes, macrophages, and eosinophils.Inflammatory cytokines, such as interleukin (IL)-1␤ and tumor necrosis factor (TNF)-␣ (5), have also been shown to be increased in nonhealing wounds. They stimulate synthesis and secretion of MMPs but inhibit the production of TIMPs (6,7). In...

show abstract

Section: Primers and Antibodiesmentioning

confidence: 99%

Section: Primers and Antibodiesmentioning

confidence: 99%

Section: -Expression (⌬Ct) Of Mmp-1 Mmp-2 Il-1␤ Tnf-␣ Cx26 and Cmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Expression of Matrix Metalloproteinases, Cytokines, and Connexins in Diabetic and Nondiabetic Human Keratinocytes Before and After Transplantation Into an Ex Vivo Wound-Healing Model

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

Wound Healing and Its Imaging

Chin

Madden

Chew

et al. 2019

Imaging Technologies and Transdermal Delivery in Skin Disorders

View full text Add to dashboard Cite

Targeting Cx26 Expression by Sustained Release of Cx26 Antisense from Scaffolds Reduces Inflammation and Improves Wound Healing

et al. 2018

View full text Add to dashboard Cite

The gap junction protein connexin 26 (Cx26) is expressed at high levels in naturally hyperthickened epidermal layers as well as pathological hyperkeratotic disease states, such as warts, psoriatic plaques, and chronic wound edges. The overexpression of Cx26 is also linked with inflammation, breakdown of the skin barrier function, and perturbed wound healing. Here, a collagen scaffold implanted into a rat excisional skin wound is used. This induces a foreign body type reaction characterized by epidermal thickening with elevated levels of Cx43 and Cx26, increased inflammation, and perturbed healing. This is reminiscent of a chronic skin wound. If the same scaffolds are coated with an antisense molecule specifically targeting Cx26 that has a slow sustained release, this prevents the abnormal upregulation of Cx26 protein at the wound edge. Knocking down Cx26 protein levels below those seen in normal wound healing has no adverse effects on the healing process but instead reduces the epidermal thickening and also the inflammatory response, while at the same time promotes the healing response. Treatment with Cx43/26 antisense may promote healing of chronic wounds. The Cx26 antisense may also be helpful in treating other skin conditions where Cx26 is overexpressed.

show abstract

Connexins 26, 30, and 43: Differences Among Spontaneous, Chronic, and Accelerated Human Wound Healing

Cited by 127 publications

References 48 publications

Expression of Matrix Metalloproteinases, Cytokines, and Connexins in Diabetic and Nondiabetic Human Keratinocytes Before and After Transplantation Into an Ex Vivo Wound-Healing Model

Expression of Matrix Metalloproteinases, Cytokines, and Connexins in Diabetic and Nondiabetic Human Keratinocytes Before and After Transplantation Into an Ex Vivo Wound-Healing Model

Wound Healing and Its Imaging

Targeting Cx26 Expression by Sustained Release of Cx26 Antisense from Scaffolds Reduces Inflammation and Improves Wound Healing

Contact Info

Product

Resources

About