Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway

Guo, Juan; Li, Yin; Yongquan, Chen; Jin, Xiaoju; Zhou, Xun; Zhu, Ni; Liu, Xiaoqian; Wei, Han-Wei; Duan, Li-Shuang

doi:10.1186/s12964-018-0290-6

Cited by 45 publications

(33 citation statements)

References 45 publications

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“…24 A previous study conducted by Chen et al demonstrated that lncRNA H19 expression is enhanced in diabetic mice. 25 FBN1, a 350-kDa glycoprotein, has been emphasized to be involved in the establishment of elastic fibers or micro-fibrils delivering strength and flexibility to connective tissues. 26 FBN1 was F I G U R E 5 Silencing of lncRNA H19 impedes wound healing in DFU mice.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA H19 acts as a miR‐29b sponge to promote wound healing in diabetic foot ulcer

Zhou

Chen

et al. 2020

FASEB j.

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Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)-29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM-related lncRNAs were initially screened by microarray data analysis. DFU models were then induced in DM mouse models. The functional role and interaction of lncRNA H19, miR-29b and FBN1 in DFU were subsequently determined by examining the proliferation, migration, and apoptosis of fibroblasts after silencing H19, inhibiting or overexpressing miR-29b and FBN1. According to microarray-based analysis, lncRNA H19 was upregulated in DM. In the ulcerative edge tissues of DFU, high expression of lncRNA H19 and FBN1 and low expression of miR-29b were observed. FBN1 was identified to be a target gene of miR-29b. LncRNA H19 could competitively bind to miR-29b, and then, inhibited its expression, which consequently upregulating FBN1. Silencing of lncRNA H19 led to inhibited proliferation, migration, and enhanced apoptosis of fibroblasts, accompanied by downregulated FBN1 but upregulated miR-29b, which diminished the expression of TGF-β1, Smad3, FN, and Col-1 and reduced extracellular matrix accumulation. Altogether, upregulation of lncRNA H19 can elevate the expression of FBN1 through competitively binding to miR-29b, which enhances the proliferation, migration, and inhibits apoptosis of fibroblasts, thus facilitating the wound healing of DFU.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA H19 acts as a miR‐29b sponge to promote wound healing in diabetic foot ulcer

Zhou

Chen

et al. 2020

FASEB j.

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“…The expression of HIF‐lα in reinjected allogeneic blood cells has been demonstrated to enhance the healing of wounds in diabetic mice, while acting to induce the angiogenesis and infiltration of macrophages in the wound beds; VEGF‐A induced by macrophages has also been shown to accelerate angiogenesis . Recent studies have revealed that the HIF‐lα pathway activation underlay the promotive effects of H19 on the activation of fibroblasts, as well as augmenting the effects associated with transfusion with improved autologous blood on the postoperative wound healing in diabetic mice . Existing literature has suggested that Ft1 promotes angiogenesis through HIF‐1α‐triggered expression and secretion of VEGF.…”

Section: Discussionmentioning

confidence: 99%

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF‐1α pathway by improving the blood preservation solution

Zhu

Yongquan

et al. 2020

FASEB j.

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Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF‐1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF‐1α pathway were determined by measuring expression of VEGF, EGF, HIF‐1α, and HSP‐90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF‐1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α‐SMA in skin tissues, and reduced TNF‐α, IL‐1β, and IL‐6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF‐1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF‐1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF‐1α pathway.

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“…Mechanistically, they showed that H19 increased the expression of the angiogenic protein HIF-1α in fibroblasts by methylating histones via H3K4me3. 28 Another transfusion study by Liu et al investigated the effects of autologous blood transfusions on wound healing in a similar diabetic mouse model. Mice treated with autologous blood efficacious in speeding wound healing showed increased levels of lncRNA MALAT1, which was found to activate fibroblasts through the initiation of the HIF-1α signaling pathway.…”

Section: Integumentary Systemmentioning

confidence: 99%

“…Guo et al utilized autologous blood transfusions in a streptozocin‐induced diabetic mouse model in which lncRNA H19 was upregulated, improving wound healing. Mechanistically, they showed that H19 increased the expression of the angiogenic protein HIF‐1α in fibroblasts by methylating histones via H3K4me3 28 . Another transfusion study by Liu et al investigated the effects of autologous blood transfusions on wound healing in a similar diabetic mouse model.…”

Section: Therapeutic Activity Of Lncrna For Tissue Repair and Regenermentioning

confidence: 99%

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

Born

Harmon

Jay

2020

Bioengineering & Transla Med

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Both extracellular vesicles (EVs) and long noncoding RNAs (lncRNAs) have been increasingly investigated as biomarkers, pathophysiological mediators, and potential therapeutics. While these two entities have often been studied separately, there are increasing reports of EV-associated lncRNA activity in processes such as oncogenesis as well as tissue repair and regeneration. Given the powerful nature and emerging translational impact of other noncoding RNAs such as microRNA (miRNA) and small interfering RNA, lncRNA therapeutics may represent a new frontier. While EVs are natural vehicles that transport and protect lncRNAs physiologically, they can also be engineered for enhanced cargo loading and therapeutic properties. In this review, we will summarize the activity of lncRNAs relevant to both tissue repair and cancer treatment and discuss the role of EVs in enabling the potential of lncRNA therapeutics. K E Y W O R D S exosomes, extracellular vesicles, lncRNA, microparticles, microvesicles lncRNAs play diverse regulatory roles in normal physiological processes. Thus, delivery of lncRNAs via EVs may help in the treatment Abbreviations: CRCs, colorectal carcinoma cells; EVs, extracellular vesicles; hAD-MSCs, human adipose-derived mesenchymal stem cells; HCAECs, human coronary artery endothelial cells; HCC, hepatocellular carcinoma cell; HDFs, human dermal fibroblasts; HDMECs, human dermal microvascular endothelial cells; lncRNA, long noncoding RNA; miRNA, microRNA; SCCs, squamous carcinoma cells.

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Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway

Cited by 45 publications

References 45 publications

Long noncoding RNA H19 acts as a miR‐29b sponge to promote wound healing in diabetic foot ulcer

Long noncoding RNA H19 acts as a miR‐29b sponge to promote wound healing in diabetic foot ulcer

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF‐1α pathway by improving the blood preservation solution

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

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