Dedicator of Cytokinesis 5 Regulates Keratinocyte Function and Promotes Diabetic Wound Healing

Qu, Hua; Tian, Miao; Wang, Yuren; Tan, Liang; Huang, Bangliang; Zhang, Linlin; Liu, Xiufei; Long, Min; Zhang, Rui; Liao, Xiaoyu; Gong, Xin; Ju, Wang; Xiong, Xin; Xi, Li; Jiang, Yu; Yang, Gangyi; Zhu, Zhiming; Wang, Cong-Yi; Zheng, Yi

doi:10.2337/db20-1008

Cited by 17 publications

(9 citation statements)

References 58 publications

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“…Protein ubiquitination has been shown to play diverse regulatory roles in the context of wound healing [ 28 , 29 ]. USP family proteins, including USP15, are key mediators of protein deubiquitination.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Platelet‐Rich Plasma‐Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

Yan

Lin

et al. 2021

Oxidative Medicine and Cellular Longevity

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Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Platelet‐Rich Plasma‐Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

Yan

Lin

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Moreover, the dedicator of cytokinesis protein (DOCK) also plays a key role in regulating keratinocyte function and promoting skin wound healing. [ 60 ] Specifically, DOCK5 regulates keratinocyte adhesion, migration, and proliferation and influences ECM deposition by laminin‐332/integrin signaling. In addition, fibroblasts showed premature senescence, abnormal morphology, and decreased ability to migrate and proliferate in diabetic wounds.…”

Section: Ros Homeostasis and Relevance Of Ros In Diabetic Woundsmentioning

confidence: 99%

Reactive Oxygen Species‐Scavenging Nanosystems in the Treatment of Diabetic Wounds

Xiong

Chu

et al. 2023

Adv Healthcare Materials

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Diabetic wounds are characterized by drug‐resistant bacterial infections, biofilm formation, impaired angiogenesis and perfusion, and oxidative damage to the microenvironment. Given their complex nature, diabetic wounds remain a major challenge in clinical practice. Reactive oxygen species (ROS), which have been shown to trigger hyperinflammation and excessive cellular apoptosis, play a pivotal role in the pathogenesis of diabetic wounds. ROS‐scavenging nanosystems have recently emerged as smart and multifunctional nanomedicines with broad synergistic applicability. The documented anti‐inflammatory and pro‐angiogenic ability of ROS‐scavenging treatments predestines these nanosystems as promising options for the treatment of diabetic wounds. Yet, in this context, the therapeutic applicability and efficacy of ROS‐scavenging nanosystems remain to be elucidated. Herein, the role of ROS in diabetic wounds is deciphered, and the properties and strengths of nanosystems with ROS‐scavenging capacity for the treatment of diabetic wounds are summarized. In addition, the current challenges of such nanosystems and their potential future directions are discussed through a clinical‐translational lens.

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“…Dedicator of cytokinesis 5 (Dock5) is one of the candidate molecules known to be implicated in proteinprotein interactions (20). Recently, Hua Qu et al found Dock5 regulated keratinocyte migration by promoting ubiquitination of ZEB1 to activate laminin-332/integrin signaling (21).…”

Section: Delayed Re-epithelialization and Collagen Depositionmentioning

confidence: 99%

The role of mesenchymal stem cell-derived EVs in diabetic wound healing

Jiang

et al. 2023

Front. Immunol.

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Diabetic foot is one of the most common complications of diabetes, requiring repeated surgical interventions and leading to amputation. In the absence of effective drugs, new treatments need to be explored. Previous studies have found that stem cell transplantation can promote the healing of chronic diabetic wounds. However, safety issues have limited the clinical application of this technique. Recently, the performance of mesenchymal stem cells after transplantation has been increasingly attributed to their production of exocrine functional derivatives such as extracellular vesicles (EVs), cytokines, and cell-conditioned media. EVs contain a variety of cellular molecules, including RNA, DNA and proteins, which facilitate the exchange of information between cells. EVs have several advantages over parental stem cells, including a high safety profile, no immune response, fewer ethical concerns, and a reduced likelihood of embolism formation and carcinogenesis. In this paper, we summarize the current knowledge of mesenchymal stem cell-derived EVs in accelerating diabetic wound healing, as well as their potential clinic applications.

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Dedicator of Cytokinesis 5 Regulates Keratinocyte Function and Promotes Diabetic Wound Healing

Cited by 17 publications

References 58 publications

[Retracted] Platelet‐Rich Plasma‐Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

[Retracted] Platelet‐Rich Plasma‐Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

Reactive Oxygen Species‐Scavenging Nanosystems in the Treatment of Diabetic Wounds

The role of mesenchymal stem cell-derived EVs in diabetic wound healing

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