Effect of matrix metalloproteinases on the healing of diabetic foot ulcer: A systematic review

Zhang, Wan-Qing; Tang, Wen; Hu, Shi‐Qi; Fu, Xue‐Lei; Wu, Hua; Shen, Weixiao; Chen, Honglin

doi:10.1016/j.jtv.2022.12.001

Cited by 8 publications

(3 citation statements)

References 45 publications

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“…It is well established that MMPs are dysregulated in diabetic healing (26), whereby MMPs are overexpressed and overactivated, along with a concomitant decrease in their inhibitors (27)(28)(29). This imbalance has been shown to inhibit proper keratinocyte migration and delay healing (30)(31)(32). We focused specifically on MMP-10 or stromelysin 2 as it was the most significantly decreased gene in the setting of A. faecalis treatment and was up-regulated by the pathogen S. aureus.…”

Section: Discussionmentioning

confidence: 99%

Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds

White,

Uberoi,

Pan

et al. 2024

Sci. Adv.

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Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on Alcaligenes faecalis , a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

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Section: Discussionmentioning

confidence: 99%

Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds

White,

Uberoi,

Pan

et al. 2024

Sci. Adv.

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show abstract

“…It is well established that MMPs are dysregulated in diabetic healing (26), whereby MMPs are overexpressed and over activated, along with a concomitant decrease in their inhibitors (27)(28)(29). This imbalance has been shown to inhibit proper keratinocyte migration and delay healing (30)(31)(32). We focused specifically on MMP-10, or stromelysin-2, as it was the most significantly decreased gene in the setting of A. faecalis treatment and was upregulated by the pathogen S. aureus.…”

Section: Discussionmentioning

confidence: 99%

Wound microbiota-mediated correction of matrix metalloproteinase expression promotes re-epithelialization of diabetic wounds

White,

Uberoi,

Pan

et al. 2023

Preprint

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Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here we focused on Alcaligenes faecalis, a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes re-epithelialization of diabetic keratinocytes, a process which is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

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“…Non-healed ulcers exhibit elevated levels of MMP-1, -2, -8, and -9, while showing lower levels of TIMP-1. This disparity in the ratio between MMPs and TIMP-1 contributes to the development of chronic ulcers, and a deficiency in the expression of MMPs can hinder the proper and timely healing of ulcers [127].…”

Section: The Inflammatory Function Of Matrix Metalloproteinases In Hu...mentioning

confidence: 99%

Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease

Costa,

Scalise,

Ielapi

et al. 2024

Biomolecules

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Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients’ social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with “sociomarkers” to develop mathematical predictive models.

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Effect of matrix metalloproteinases on the healing of diabetic foot ulcer: A systematic review

Cited by 8 publications

References 45 publications

Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds

Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds

Wound microbiota-mediated correction of matrix metalloproteinase expression promotes re-epithelialization of diabetic wounds

Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease

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