Dysregulation of collagen production in diabetes following recurrent skin injury: Contribution to the development of a chronic wound

Caskey, Robert C.; Zgheib, Carlos; Morris, Michael W.; Allukian, Myron; Dorsett‐Martin, Wanda; Xu, Jie; Wu, Wenjie; Liechty, Kenneth W.

doi:10.1111/wrr.12199

Cited by 28 publications

(20 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…to the low collagen content detected in diabetic wounds. 25,26 Similarly, the NO precursor arginine failed to respond to injury in diabetic wounds (Table 3), which supports previous studies demonstrating reduced NO synthesis in diabetic wounds. 27 It may also explain why arginine supplementation improves wound healing in diabetes.…”

Section: Discussionsupporting

confidence: 85%

“…Our metabolomics data are consistent with well‐documented impaired responses to injury in diabetic wounds including reduced collagen synthesis and reduced nitric oxide (NO) production . Known indices of collagen synthesis, proline and hydroxyproline, had no response to injury in diabetic wounds (Table ), which may contribute to the low collagen content detected in diabetic wounds . Similarly, the NO precursor arginine failed to respond to injury in diabetic wounds (Table ), which supports previous studies demonstrating reduced NO synthesis in diabetic wounds .…”

Section: Discussionsupporting

confidence: 84%

See 1 more Smart Citation

Targeted metabolic profiling of wounds in diabetic and nondiabetic mice

Sood

Djukovic

et al. 2015

Wound Repair Regeneration

View full text Add to dashboard Cite

While cellular metabolism is known to regulate a number of key biological processes such as cell growth and proliferation, its role in wound healing is unknown. We hypothesized that cutaneous injury would induce significant metabolic changes and that the impaired wound healing seen in diabetes would be associated with a dysfunctional metabolic response to injury. We used a targeted metabolomics approach to characterize the metabolic profile of uninjured skin and full-thickness wounds at day 7 postinjury in nondiabetic (db/-) and diabetic (db/db) mice. By liquid chromatography mass spectrometry, we identified 129 metabolites among all tissue samples. Principal component analysis demonstrated that uninjured skin and wounds have distinct metabolic profiles and that diabetes alters the metabolic profile of both uninjured skin and wounds. Examining individual metabolites, we identified 62 with a significantly altered response to injury in the diabetic mice, with many of these, including glycine, kynurenate, and OH-phenylpyruvate, implicated in wound healing for the first time. Thus, we report the first comprehensive analysis of wound metabolic profiles, and our results highlight the potential for metabolomics to identify novel biomarkers and therapeutic targets for improved wound healing outcomes.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 84%

Targeted metabolic profiling of wounds in diabetic and nondiabetic mice

Sood

Djukovic

et al. 2015

Wound Repair Regeneration

View full text Add to dashboard Cite

show abstract

“…Extracellular matrix (ECM) synthesis, assembly, and organization occur during the latter two phases and are essential for restoring tissue strength and structure (Singer and Clark, 1999). Dermal fibroblasts are the main cell type responsible for ECM synthesis, and dysfunctional matrix deposition has been implicated in both chronic, nonhealing wounds and scar formation (Caskey et al, 2014;Herrick et al, 1992;Xue and Jackson, 2013). Deciphering the function of specific regulatory molecules involved in these processes could offer new insights into impaired wound healing and identify therapeutic targets for wound repair and tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility

Theocharidis

Drymoussi

Kao

et al. 2016

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Type VI collagen is a non-fibrillar collagen expressed in many connective tissues and implicated in extracellular matrix (ECM) organisation. We hypothesized that type VI collagen regulates matrix assembly and cell function within the dermis of the skin. In the present study we examined the expression pattern of type VI collagen in normal and wounded skin and investigated its specific function in new matrix deposition by human dermal fibroblasts. Type VI collagen was expressed throughout the dermis of intact human skin, at the expanding margins of human keloid samples, and in the granulation tissue of newly deposited ECM in a mouse model of wound healing. Generation of cell derived matrices (CDMs) by human dermal fibroblasts with stable knockdown of COL6A1 revealed that type VI collagen deficient matrices were significantly thinner and contained more aligned, thicker, and widely spaced fibres than CDMs produced by normal fibroblasts. In addition, there was significantly less total collagen and sulfated proteoglycans present in the type VI collagen depleted matrices. Normal fibroblasts cultured on de-cellularised CDMs lacking type VI collagen displayed increased cell spreading, migration speed, and persistence. Taken together, these findings indicate that type VI collagen is a key regulator of dermal matrix assembly, composition, and fibroblast behaviour and may play an important role in wound healing and tissue regeneration.Journal of Investigative Dermatology accepted article preview online, 09 September 2015. doi:10.1038/jid.2015.352.

show abstract

“…Here we discuss data that demonstrate correction of microRNA dysregulation expedites wound healing and reverses the diabetic phenotype in skin [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

The Role of MicroRNAs in Impaired Diabetic Wound Healing

Hodges¹,

Zgheib²,

Xu³

et al. 2016

Wound Healing - New Insights Into Ancient Challenges

Self Cite

View full text Add to dashboard Cite

Diabetes mellitus is a worldwide pandemic, affecting 29 million Americans, resulting in substantial morbidity and mortality, and accounting for an annual healthcare expenditure exceeding $176 billion in the US alone. This burden of disease is the result of a progressive disease associated with numerous complications and the development of chronic wounds, which remain the leading cause of hospital admissions and nontraumatic lower extremity amputations in diabetic patients. Despite clinical strategies aimed at prevention and early detection, patients with diabetes continue to remain at risk of developing chronic diabetic wounds due to poor patient compliance and progression of the diabetic phenotype. Development of the diabetic phenotype and wound healing impairment is associated with dysregulation of microRNAs that regulate inflammation, extracellular matrix composition, and angiogenesis; here we present evidence from the studies that demonstrate correction of microRNA dysregulation expedites wound healing and reverses the diabetic skin phenotype.

show abstract

Dysregulation of collagen production in diabetes following recurrent skin injury: Contribution to the development of a chronic wound

Cited by 28 publications

References 20 publications

Targeted metabolic profiling of wounds in diabetic and nondiabetic mice

Targeted metabolic profiling of wounds in diabetic and nondiabetic mice

Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility

The Role of MicroRNAs in Impaired Diabetic Wound Healing

Contact Info

Product

Resources

About