Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

Liu, Yan; Dhall, Sandeep; Castro, Anthony; Chan, Alex; Alamat, Raquelle; Martins‐Green, Manuela

doi:10.1242/bio.026187

Cited by 30 publications

(24 citation statements)

References 34 publications

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“…In addition, a direct interaction of the complement modulator CD46 with SPAK was shown to induce cell proliferation and to accelerate wound healing of Caco‐2 intestinal epithelial cells thereby suggesting a role for SPAK in the regulation of the epithelial cell barrier integrity and repair (Cardone, Al‐Shouli, & Kemper, ). More recently, results by Y. Liu et al () suggested that SPAK activation, through insulin‐induced chemotaxis of THP‐1 cells, may also contribute to insulin‐driven wound healing.…”

Section: Discussionmentioning

confidence: 99%

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Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Desjardins

Couture

Germain

et al. 2019

J Tissue Eng Regen Med

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Damage to the corneal epithelium triggers important changes in the extracellular matrix (ECM) to which basal human corneal epithelial cells (hCECs) attach. These changes are perceived by integrin receptors that activate different intracellular signalling pathways, ultimately leading to re‐epithelialization of the injured epithelium. In this study, we investigated the impact of pharmacological inhibition of specific signal transduction mediators on corneal wound healing using both monolayers of hCECs and the human tissue‐engineered cornea (hTEC) as an in vitro 3D model. RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The impact of WNK1 inhibition was evaluated on the wounded hTECs as well as on hCECs monolayers using a scratch wound assay. Gene profiling and protein kinase arrays revealed that expression and activity of several mediators from the integrin‐dependent signaling pathways were altered in response to the ECM changes occurring during corneal wound healing. Phosphorylation of the WNK1 kinase turned out to be the most striking activation event going on during this process. The inhibition of WNK1 by WNK463 reduced the rate of corneal wound closure in both the hTEC and hCECs grown in monolayer compared with their respective negative controls. WNK463 also reduced phosphorylation of the WNK1 downstream targets SPAK/OSR1 in wounded hTECs. These in vitro results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and identified WNK1 as a kinase important to ensure proper wound healing of the cornea.

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Section: Discussionmentioning

confidence: 99%

“…More recently, results by Y. Liu et al (2018) suggested that SPAK activation, through insulin-induced chemotaxis of THP-1 cells, may also contribute to insulin-driven wound healing.…”

Section: Inhibition Of Wnk1 Alters the Proliferative Properties Of mentioning

confidence: 99%

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Desjardins

Couture

Germain

et al. 2019

J Tissue Eng Regen Med

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“…Insulin-induced keratinocyte migration and differentiation are insulin receptor-dependent, but EGFR-dependent; moreover, this effect is mediated through the PI3K-Akt-Rac1 pathway. 18 Topical insulin treatment on burnt skin improves collagen deposition and maturation, as evidenced by increased hydroxyproline levels. 16 In addition to regulating re-epithelialization and inflammatory responses at wound tissues, insulin also exerts angiogenic effect on wounds.…”

Section: Mechanisms Of the Effect Of Topical Insulin On Wound Healingmentioning

confidence: 99%

<p>Effects of Topical Insulin on Wound Healing: A Review of Animal and Human Evidences</p>

Wang

2020

DMSO

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Wound healing is a complex biological process that repairs damaged tissues and restores skin integrity. Insulin, a potent factor of wound healing, has been reported for nearly a century to induce rapid recovery of various wounds, as shown by numerous human and animal studies. Although many studies have addressed the healing effect of systemic insulin on burn wound, only few have investigated the efficacy of topical insulin. Thus, this study aimed to review evidence of the effects of topical insulin on wound healing, including on diabetic and non-diabetic wounds. The presented animal and clinical studies support that topical insulin improves wound healing through several mechanisms without causing side effects. Additionally, various wound dressings accelerate the wound healing with controlled and sustained delivery of bioactive insulin. Therefore, topical insulin has been appreciated in field of wound healing, and further studies are needed to improve our understanding of the role of insulin in the healing of various wounds.

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“…The phosphorylation of AKT Thr 308 regulates the activity of Rac-1 through PDK1 (Higuchi et al, 2008, Niba et al, 2013, Liu et al, 2018). There is an increase in the activity of RAC-1 and the phosphorylation of AKT by stimulation with growth factors, as in the cell line MDA-MB-231 (mammary gland epithelial cells) treated with epidermal growth factor (EGF) (Yang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Myo1e modulates the recruitment of B cells to inguinal lymph nodes

Girón-Pérez

Santos-Argumedo

Vadillo

et al. 2019

Preprint

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The recruitment of leukocyte to high endothelium venules and their migration to the lymph nodes are critical steps to initiate an immune response. Cell migration is regulated by the actin cytoskeleton where myosins have a very import role. Myo1e is a long tail class I myosin highly expressed in B cells that not have been studied in the context of cell migration. By using an in vivo model, through the use of intravital microscopy, we demonstrated the relevance of Myo1e in the adhesion and the migration of B cells in high endothelial venules. These observations were confirmed by in vitro experiments. We also registered a reduction in the expression of integrins and F-actin in the protrusion of B lymphocytes membrane. Deficiencies in vesicular trafficking can explain the decrease of integrins on the surface. Interestingly, Myo1e is associated with focal adhesion kinase (FAK). The lack of Myo1e affected the phosphorylation of FAK and AKT, and the activity of RAC-1, disturbing the FAK/PI3K/RAC-1 signaling pathway. Together, our results indicate critical participation of Myo1e in the mechanism of B cell migration.Summary statementMyo1e participate in the adhesion and migration in the high endothelial venules by regulation of integrins and the PI3K/FAK/RAC-1 signaling pathway.

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Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

Cited by 30 publications

References 34 publications

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

<p>Effects of Topical Insulin on Wound Healing: A Review of Animal and Human Evidences</p>

Myo1e modulates the recruitment of B cells to inguinal lymph nodes

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