Protective effect of mesenchymal stem cells on the pressure ulcer formation by the regulation of oxidative and endoplasmic reticulum stress

Motegi, Sei‐ichiro; Sekiguchi, Akiko; Uchiyama, Akihiko; Uehara, Akihito; Fujiwara, Chisako; Yamazaki, Sunao; Perera, Buddhini; Nakamura, Hideharu; Ogino, Sachiko; Yokoyama, Yoko; Akai, Ryoko; Ishikawa, Osamu

doi:10.1038/s41598-017-17630-5

Cited by 42 publications

(63 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypoxic tissue damage caused by impaired blood circulation in local tissue is considered to be the major mechanism of PU . In this regard, local compression and hypoxia can cause a series of pathological reactions, such as impaired energy metabolism, generation of oxygen radicals, lipid peroxidation, inflammatory cell infiltration, and intracellular Ca 2+ overload, resulting in local tissue damage . in vitro cell model are often a combination of mimicking cellular environment in PU.…”

Section: Discussionmentioning

confidence: 99%

“…*p < .05, **p < .01, or ***p < .001 hinted the significant difference between indicated group oxygen radicals, lipid peroxidation, inflammatory cell infiltration, and intracellular Ca 2+ overload, resulting in local tissue damage. 29 in vitro cell model are often a combination of mimicking cellular environment in PU. Here, hypoxic treatment, known to trigger inflammation, 30 is often used in PU-related research studies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Wang

Liu

et al. 2020

IUBMB Life

View full text Add to dashboard Cite

Background Pressure ulcer (PU) is a common complication of acute and long‐time hospitalization, especially in elderly patients. The incidence and prevalence of PU are swiftly fortifying. Currently, our purpose was to investigate the functional impacts of circ‐Ttc3 on PU. Methods HaCaT cells were pretreated under hypoxia condition. Cell counting kit 8 assay and flow cytometry were utilized to test HaCaT cell viability and apoptosis. Quantitative reverse transcription polymerase chain reaction was utilized to determine circ‐Ttc3 and miR‐449a expression. Western blot was performed to examine apoptosis‐associated proteins expression. Subsequently, the above‐described investigations were reperformed after miR‐449a upregulation. Results Hypoxia induced apoptosis and declined viability in HaCaT cells. Circ‐Ttc3 expression was enhanced after transfection with circ‐Ttc3 expressing vector. Overexpressing circ‐Ttc3 raised viability and reduced apoptosis in HaCaT cells. Moreover, miR‐449a expression was elevated by hypoxia and reversed by overexpressing circ‐Ttc3. And circ‐Ttc3 exerted its effect via downregulating miR‐449a. Finally, overexpressing circ‐Ttc3 activated nuclear factor kappa‐B (NF‐κB) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathways via downregulating miR‐449a. Conclusion Our data suggested that circ‐Ttc3 alleviated hypoxic injury and activated NF‐κB and PI3K/AKT pathways by downregulating miR‐449a in HaCaT cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Wang

Liu

et al. 2020

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…role in the apoptosis of various types of cells in models of ischemia in vivo and in vitro (26). Furthermore, MSCs are susceptible to apoptosis induced by ER stress, and blockage of ER stress promoted the survival of MSCs under H/SD conditions (27). In response to ER stress, there is an upregulation of ER chaperones such as CHOP and ATF4 (28).…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells

Shi

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad-spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti-inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation-induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) family proteins, total-Akt and phospho-Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase-3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl-2, Bcl-extra large and Bcl-associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI-induced anti-apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.

show abstract

“…injection of apelin protected vascular loss by cutaneous i/R injury. We previously identified that the number of blood vessels was reduced after cutaneous I/R injury in mice 20 . Therefore, we investigated the effect of apelin on vascular loss caused by cutaneous I/R injury.…”

Section: Apelin Protected Pus Formation After Cutaneous I/r In Mice Mmentioning

confidence: 99%

“…After that ROS levels was measured with DCFDA Cellular ROS Detection Assay Kit (abcam, Cambridge, UK) according to the manufacturer's protocol with fluorescent microplate measurement.Apoptosis and necrosis analysis with flow cytometry. Flow cytometric analysis of apoptosis was performed as described previously 20,44 . NIH3T3 cells were incubated in control medium or apelin with or without H 2 O 2 (0.75 mM) for 24 hours before apoptosis analysis through flow cytometry.…”

mentioning

confidence: 99%

Apelin/APJ signaling suppresses the pressure ulcer formation in cutaneous ischemia-reperfusion injury mouse model

Yamazaki

Sekiguchi

Uchiyama

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Several studies have demonstrated potential roles for apelin/ApJ signaling in the regulation of oxidative stress associated with ischemia-reperfusion (i/R) injury in several organs. objective was to assess the role of apelin/ApJ signaling in the development of pressure ulcers (pUs) formation after cutaneous i/R injury in mice. We identified that cutaneous I/R injury increased the expression of apelin in the skin at I/R site. Administration of apelin significantly inhibited the formation of PUs. The reductions of blood vessels, hypoxic area and apoptosis in i/R site were inhibited by apelin injection. oxidative stress signals in OKD48 mice and the expressions of oxidative stress related genes in the skin were suppressed by apelin injection. H 2 o 2 -induced intracellular ROS and apoptosis in endothelial cells and fibroblasts were suppressed by apelin in vitro. Furthermore, MM07, biased agonist of APJ, also significantly suppressed the development of PUs after cutaneous I/R, and the inhibitory effect of MM07 on PUs formation was higher than that in apelin. We conclude that apelin/ApJ signaling may inhibit cutaneous i/R injuryinduced pUs formation by protecting the reduction of vascularity and tissue damage via suppression of oxidative stress. Exogenous application of apelin or MM07 might have therapeutic potentials against the development of pUs.Pressure ulcers (PUs) are one of the common skin diseases which usually occur elder people and patients with perceptual or movement disorder. In addition, the patients with PUs sometimes cause fatal outcome by local and systemic infections. There has long been considered that the pathogenesis of PUs was associated with tissue damage caused by external force and ischemia. However, there has been increasing evidence that cutaneous ischemia-reperfusion (I/R) is important in the pathogenesis of PUs 1-3 . I/R injury is defined as cellular injury caused by the reperfusion of blood to previously ischemic tissue 4,5 . It is described that reperfusion of blood into the hypoxic tissue triggers off adverse events, including thrombosis and capillary narrowing which lead to vasculopathy, infiltration of inflammatory cells, production of proinflammatory cytokines and the apoptosis of resident cells and necrosis of tissues 6 . I/R injury causes multiple diseases, such as vascular infarction or spasm of brain, heart, kidney and skin. Reactive oxygen species (ROS), such as H 2 O 2 and NO, are also known as a key player that exacerbate the tissues damage caused by I/R injury 7 .Apelin, an endogenous ligand of G protein-coulpled receptor APJ (putative receptor protein related to the angiotensin receptor AT1) 8,9 has multiple functions in the regulation of cardiovascular hemostasis, angiogenesis and adipose tissue function via apelin/APJ signaling 10-13 . APJ is expressed ubiquitously, especially in endothelial cells and vascular smooth muscle cells 8,9,11,12 . Furthermore, recent studies demonstrated that apelin/APJ signaling prevented oxidative stress, resulting in the inhibition of diabetic...

show abstract

Protective effect of mesenchymal stem cells on the pressure ulcer formation by the regulation of oxidative and endoplasmic reticulum stress

Cited by 42 publications

References 52 publications

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells

Apelin/APJ signaling suppresses the pressure ulcer formation in cutaneous ischemia-reperfusion injury mouse model

Contact Info

Product

Resources

About