title: Dysregulation of collagen production in diabetes following recurrent skin injury: contribution to the development of a chronic wound.
abstract: Recurrent injury has been implicated in the development of chronic diabetic wounds. We have developed a chronic diabetic wound model based upon recurrent injury in diabetic mice. We hypothesized that dysregulation of collagen production at both the mRNA and microRNA levels contributes to the development of chronic diabetic wounds. To test this, both diabetic and nondiabetic mice were made to undergo recurrent injury. Real-time PCR for TGF-β1, SMAD-3, Col1α1, Col3α1, microRNA-25, and microRNA-29a and Western blot for collagen I and III were performed 7 days following each injury. Diabetic wounds displayed decreased collagen at all time points. This was associated with dysregulated collagen production at both the gene and microRNA levels at all time points. Following the final injury, however, diabetic collagen production significantly improved. This appeared to be due to a substantial decrease in both microRNAs as well as an increase in the expression of collagen pathway genes. That dysregulated collagen production progressed throughout the course of wounding suggests that this is one factor contributing to the development of chronic diabetic wounds. Future studies using this model will allow for the determination of other factors that may also contribute to the development and/or persistence of chronic diabetic wounds.
authors.affiliation: Department of General Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Caskey
authors.forename: Carlos
authors.initials: C
authors.lastname: Zgheib
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Myron
authors.initials: M
authors.lastname: Allukian
authors.forename: Wanda
authors.initials: W
authors.lastname: Dorsett-Martin
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D002908:Chronic Disease; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004548:Elasticity; D051379:Mice; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000293:injuries* / Q000378:metabolism*; D012883:Skin Ulcer / Q000209:etiology / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D035683:MicroRNAs; D012333:RNA, Messenger; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; D003094:Collagen