Compression‐induced HIF‐1 enhances thrombosis and PAI‐1 expression in mouse skin

Kaneko, Maki; Minematsu, Takeo; Yoshida, Mikako; Nishijima, Yoshimi; Noguchi, Hiroshi; Ohta, Yasunori; Nakagami, Gojiro; Mori, Taketoshi; Sanada, Hiromi

doi:10.1111/wrr.12312

Cited by 19 publications

(15 citation statements)

References 25 publications

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“…Moreover, emerging evidence suggests that mechanical forces can trigger HIF-1 induction. For example, HIF-1α can be induced by mechanical stretching in capillary endothelial cells 48 , by compression in skin cells 49 , and by pressure in heart ventricles 50 . HIF-1α is also upregulated in the brain cortex following traumatic brain injury 51 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

Calhoun

Cui

Elliott

et al. 2020

Sci Rep

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Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy). A prominent feature of the GBM microenvironment is compressive solid stress (CSS) caused by uninhibited tumor growth within the confined skull. Here, we utilized a mechanical compression model to apply cSS (<115 Pa) to well-characterized LN229 and U251 GBM cell lines and measured their motility, morphology, and transcriptomic response. Whereas both cell lines displayed a peak in migration at 23 Pa, cells displayed differential response to CSS with either minimal (i.e., U251) or large changes in motility (i.e., LN229). Increased migration of LN229 cells was also correlated to increased cell elongation. these changes were tied to epigenetic signaling associated with increased migration and decreases in proliferation predicted via ingenuity ® Pathway Analysis (IPA), characteristics associated with tumor aggressiveness. miRnA-mRnA interaction analysis revealed strong influence of the miR548 family (i.e., mir-548aj, mir-548az, mir-548t) on differential signaling induced by CSS, suggesting potential targets for pharmaceutical intervention that may improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

Calhoun

Cui

Elliott

et al. 2020

Sci Rep

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“…A histopathological study in non‐blanchable erythema has shown abundant fibrin thromboses in the reticular dermis and subcutaneous tissue . Kaneko et al also reported that compression of mouse skin significantly increased the number of thromboses. Consistent with these findings, we found thromboses in the dermis in the I/R site in control mice.…”

Section: Discussionmentioning

confidence: 93%

“…Cutaneous I/R injury has been reported to induce thromboses and to suppress the luminal areas of blood vessels in the dermis, as well as to induce hypoxia and oxidative stress at the I/R site . Based on these previous studies, we investigated the effects of BBP on blood vessels in the I/R area in a cutaneous I/R injury model.…”

Section: Resultsmentioning

confidence: 99%

Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia–reperfusion injury

Uchiyama

Yamada

Perera

et al. 2016

Experimental Dermatology

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Ischaemia-reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. However, there is no evidence-based treatment for early-stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31(+) vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68(+) macrophages and the level of transforming growth factor-beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress-induced tissue damage. Topical steroids might not be recommended for the treatment of acute-phase decubitus ulcers.

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“…First, the study has employed a murine skin wound ischemia reperfusion model of pressure injury. Although this model has been validated in multiple publications, 12–15,37–39 the translatability of findings in a murine skin model to the human condition faces some challenges. Rodent skin healing occurs in part due to contraction rather than reepithelialization.…”

Section: Discussionmentioning

confidence: 99%

A Novel, Sterilized Microvascular Tissue Product Improves Healing in a Murine Pressure Ulcer Model

Gimble

Frazier

et al. 2018

Plastic and Reconstructive Surgery - Global Open

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Background:Processed microvascular tissue (PMVT), a human structural allograft, is derived from lyophilized human tissue containing microcirculatory cellular components. Since PMVT serves as a source of extracellular matrix (ECM), growth factors, cytokines, and chemokines modulating angiogenesis, inflammation, apoptosis, and endogenous cell recruitment, we hypothesized its application would accelerate wound regeneration in a validated pressure ulcer (PU) model developed in C57BL/6 mice using two 24-hour cycles of skin ischemia/reperfusion created by placement and removal of external magnets.Methods:Two identical PU injuries (n = 50 female mice) were treated with (a) topical particulate PMVT, (b) injected rehydrated PMVT, or (c) saline control injection, and assessed daily for closure rates, scab formation/removal, and temperature. A baseline control cohort (n = 5) was euthanized at day 0 and treatment group cohorts (n = 5) were killed at 3, 7, or 14 days postinjury. The PU injuries were collagenase-digested for flow cytometric analysis of inflammatory, reparative, and stem cell frequencies and analyzed by hematoxylin and eosin (H&E) histology and immunofluorescence.Results:PMVT-accelerated wound closure, most notably, topical PMVT significantly increased mean closure from d5 (13% versus -9%) through d13 (92% versus 38%) compared with phosphate-buffered saline (PBS) controls (P < 0.05). PMVT also hastened scab formation/removal, significantly accelerated disappearance of inflammatory myeloid (CD11b+) cells while upregulating α-smooth muscle actin, vascular endothelial growth factor A, and placental growth factor and raised skin temperature surrounding the PU site, consistent with increased blood flow.Conclusions:These results indicate that PMVT has potential as an advanced treatment for restoring normal tissue function in ischemic wounds and merits clinical study.

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Compression‐induced HIF‐1 enhances thrombosis and PAI‐1 expression in mouse skin

Cited by 19 publications

References 25 publications

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia–reperfusion injury

A Novel, Sterilized Microvascular Tissue Product Improves Healing in a Murine Pressure Ulcer Model

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