Overexpression of Thioredoxin1 enhances functional recovery in a mouse model of hind limb ischemia

Shaikh, Inam A.; Rishi, Muhammad Adeel; Youssef, Mark; Selvaraju, Vaithinathan; Thirunavukkarasu, Mahesh; Ukani, Gopi; Lakshmanan, Rajesh; Palesty, J. Alexander; Maulik, Nilanjana

doi:10.1016/j.jss.2017.04.019

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Shaikh et al, revealed that Hif-1α activity depends on Trx-1 redox status. 58 Trx-1 scavenges reactive oxygen species during oxidative stress and rescues injured cells from hypoxia to maintain homeostasis. 59 As reported by Naranjo-Suarez et al, overexpression of Trx-1 in HeLa, HT-29, MCF-7, and EMT6 cell lines did not stabilize Hif-1α but led to increased activity.…”

Section: Discussionmentioning

confidence: 99%

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 ^−/− ) mice affects the skin wound healing process

et al. 2021

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Skin, the largest organ of the body, serves as a protective barrier against infections, heat loss, dehydration, and mechanical insults and can sense external (temperature, touch) and internal (neurons, hormones) signals. 1,2 Interruption of skin integrity by injury or surgical intervention can lead to severe damage and abnormal homeostasis. 3 The integrity of the wounded skin is restored through a reparative healing process, which results in scar formation. Although scarring

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Section: Discussionmentioning

confidence: 99%

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 ^−/− ) mice affects the skin wound healing process

et al. 2021

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“…Furthermore, double immunofluorescence staining showed colocalization of Trx-1 with Foxn1 in the epidermis, particularly in the suprabasal layer. Shaikh et al, revealed that Hif-1α activity depends on Trx-1 redox status (Shaikh et al, 2017). Trx-1 scavenges reactive oxygen species during oxidative stress and rescues injured cells from hypoxia to maintain homeostasis (Yamawaki, Haendeler, & Berk, 2003).…”

Section: Discussionmentioning

confidence: 99%

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

Machcińska

Kopcewicz

Bukowska

et al. 2020

Preprint

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Hypoxia and hypoxia-regulated factors [hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1)] have essential roles in skin wound healing. Using Foxn1-/- mice that can heal skin injuries in a unique scar-free manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. Foxn1-/- mice displayed impairments in the regulation of Hif-1α and Fih-1 during the healing process. An analysis of wounded skin showed that the skin of Foxn1-/- mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in Tgfβ-3 and collagen III expression. An in vitro analysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of Foxn1-/- mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, Foxn1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, Foxn1 is a limiting factor for Hif-1α.

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“…For the gene transduction experiment, mice were anesthetized to induce hind limb ischemia using a procedure consisting of the ligation of both the proximal end of the femoral artery and the distal portion of the saphenous artery. Immediately, Ad-AURKA OE or Ad-NC OE (10 9 plaque-forming unit) was delivered to the ischemic adductor muscle and gastrocnemius muscles (Shaikh et al 2017 ). The blood flow of the ischemic and the contralateral feet was sequentially measured (at 0, 3, 7, 14, 21, and 28 days post-surgery) by laser Doppler Image, and the relative perfusion ratio between the ischemic foot and non-ischemic foot was calculated.…”

Section: Methodsmentioning

confidence: 99%

The promotion action of AURKA on post-ischemic angiogenesis in diabetes-related limb ischemia

Bai

Liu

et al. 2023

Mol Med

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Background Diabetes-related limb ischemia is a challenge for lower extremity amputation. Aurora Kinase A (AURKA) is an essential serine/threonine kinase for mitosis, while its role in limb ischemia remains unclear. Method Human microvascular endothelial cells (HMEC-1) were cultured in high glucose (HG, 25 mmol/L d-glucose) and no additional growth factors (ND) medium to mimic diabetes and low growth factors deprivation as in vitro model. Diabetic C57BL/6 mice were induced by streptozotocin (STZ) administration. After seven days, ischemia was surgically performed by left unilateral femoral artery ligation on diabetic mice. The vector of adenovirus was utilized to overexpress AURKA in vitro and in vivo. Results In our study, HG and ND-mediated downregulation of AURKA impaired the cell cycle progression, proliferation, migration, and tube formation ability of HMEC-1, which were rescued by overexpressed AURKA. Increased expression of vascular endothelial growth factor A (VEGFA) induced by overexpressed AURKA were likely regulatory molecules that coordinate these events. Mice with AURKA overexpression exhibited improved angiogenesis in response to VEGF in Matrigel plug assay, with increased capillary density and hemoglobin content. In diabetic limb ischemia mice, AURKA overexpression rescued blood perfusion and motor deficits, accompanied by the recovery of gastrocnemius muscles observed by H&E staining and positive Desmin staining. Moreover, AURKA overexpression rescued diabetes-related impairment of angiogenesis, arteriogenesis, and functional recovery in the ischemic limb. Signal pathway results revealed that VEGFR2/PI3K/AKT pathway might be involved in AURKA triggered angiogenesis procedure. In addition, AURKA overexpression impeded oxidative stress and subsequent following lipid peroxidation both in vitro and in vivo, indicating another protective mechanism of AURKA function in diabetic limb ischemia. The changes in lipid peroxidation biomarkers (lipid ROS, GPX4, SLC7A11, ALOX5, and ASLC4) in in vitro and in vivo were suggestive of the possible involvement of ferroptosis and interaction between AUKRA and ferroptosis in diabetic limb ischemia, which need further investigation. Conclusions These results implicated a potent role of AURKA in diabetes-related impairment of ischemia-mediated angiogenesis and implied a potential therapeutic target for ischemic diseases of diabetes.

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Overexpression of Thioredoxin1 enhances functional recovery in a mouse model of hind limb ischemia

Cited by 9 publications

References 36 publications

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 ^−/− ) mice affects the skin wound healing process

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 ^−/− ) mice affects the skin wound healing process

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

The promotion action of AURKA on post-ischemic angiogenesis in diabetes-related limb ischemia

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Overexpression of Thioredoxin1 enhances functional recovery in a mouse model of hind limb ischemia

Cited by 9 publications

References 36 publications

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 −/− ) mice affects the skin wound healing process

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 −/− ) mice affects the skin wound healing process

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1−/−) mice affects the skin wound healing process

The promotion action of AURKA on post-ischemic angiogenesis in diabetes-related limb ischemia

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Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 ^−/− ) mice affects the skin wound healing process

Impairment of the Hif‐1α regulatory pathway in Foxn1‐deficient (Foxn1 ^−/− ) mice affects the skin wound healing process

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process