Gravitational effects on fibroblasts’ function in relation to wound healing

Radstake, Wilhelmina E.; Gautam, Kiran; Miranda, Silvana; Rompay, Cynthia Van; Vermeesen, Randy; Tabury, Kevin; Verslegers, Mieke; Dowson, Alan; Gorissen, Jeffrey; Loon, Jack J. W. A. van; Savage, Nigel D. L.; Baatout, Sarah; Baselet, Bjorn

doi:10.1038/s41526-023-00286-z

Cited by 8 publications

(1 citation statement)

References 59 publications

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“…Fibroblasts exhibit high sensitivity to SMG, which validates the possible significance of the TGF-β1/Smad3 signaling pathway in regulating wound healing [20]. A recent study revealed that changes in fibroblast structures and delayed cell migration were the main effects of altered gravity, contributing to alterations in the fibroblasts' function related to wound healing [21]. These studies indicated the gravisensitivity of mouse fibroblasts to SMG, suggesting that these cells are suitable for assessing the influence of microgravity on characteristics such as proliferation, function, and morphology.…”

Section: Discussionmentioning

confidence: 58%

Morphological Changes of 3T3 Cells under Simulated Microgravity

Tran,

Ho,

Hoang

et al. 2024

Cells

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Background: Cells are sensitive to changes in gravity, especially the cytoskeletal structures that determine cell morphology. The aim of this study was to assess the effects of simulated microgravity (SMG) on 3T3 cell morphology, as demonstrated by a characterization of the morphology of cells and nuclei, alterations of microfilaments and microtubules, and changes in cycle progression. Methods: 3T3 cells underwent induced SMG for 72 h with Gravite®, while the control group was under 1G. Fluorescent staining was applied to estimate the morphology of cells and nuclei and the cytoskeleton distribution of 3T3 cells. Cell cycle progression was assessed by using the cell cycle app of the Cytell microscope, and Western blot was conducted to determine the expression of the major structural proteins and main cell cycle regulators. Results: The results show that SMG led to decreased nuclear intensity, nuclear area, and nuclear shape and increased cell diameter in 3T3 cells. The 3T3 cells in the SMG group appeared to have a flat form and diminished microvillus formation, while cells in the control group displayed an apical shape and abundant microvilli. The 3T3 cells under SMG exhibited microtubule distribution surrounding the nucleus, compared to the perinuclear accumulation in control cells. Irregular forms of the contractile ring and polar spindle were observed in 3T3 cells under SMG. The changes in cytoskeleton structure were caused by alterations in the expression of major cytoskeletal proteins, including β-actin and α-tubulin 3. Moreover, SMG induced 3T3 cells into the arrest phase by reducing main cell cycle related genes, which also affected the formation of cytoskeleton structures such as microfilaments and microtubules. Conclusions: These results reveal that SMG generated morphological changes in 3T3 cells by remodeling the cytoskeleton structure and downregulating major structural proteins and cell cycle regulators.

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Section: Discussionmentioning

confidence: 58%

Morphological Changes of 3T3 Cells under Simulated Microgravity

Tran,

Ho,

Hoang

et al. 2024

Cells

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Naturally Inspired Tree‐Ring Structured Dressing Provides Sustained Wound Tightening and Accelerates Closure

Chen,

Zhang,

Zhang

et al. 2024

Advanced Materials

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Mechanically regulated wound dressings require a rational combination of contraction and adhesion functions as well as balancing exudate‐induced swelling issues. However, many of the reported dressings face the dilemma of impaired function and impeded wound self‐contraction due to fluid‐absorbing swelling. In this study, inspired by the tree ring, a core–ring structured hydrogel dressing capable of mechanical modulation is designed, and prepare it using a simple two‐step photopolymerization process. The core covers the center of the wound, contracts spontaneously at body temperature to generate a contractile force of 3.4 kPa, and resists swelling. Meanwhile, the ring adheres to the normal epidermis around the wound and transfers the contraction stress to the wound edge. The integration of a functionally independent core and ring ultimately achieves effective wound traction and avoids dressing swelling. In murine and porcine skin wound‐healing models, this hydrogel with a closely connected core and ring promotes healing by accelerating epidermal closure (50% closure in mouse skin on day 2, 85% closure in pig skin on day 8), collagen deposition, vascular maturation, and extracellular matrix remodeling. These results can guide further research on mechanical force modulation in wound healing, with the potential for clinical translation.

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Simulated microgravity attenuates skin wound healing by inhibiting dermal fibroblast migration via F‐actin/YAP signaling pathway

Zhou,

Lv,

Peng

et al. 2023

Journal Cellular Physiology

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Skin and its cell components continuously subject to extrinsic and intrinsic mechanical forces and are mechanical sensitive. Disturbed mechanical homeostasis may lead to changes in skin functions. Gravity is the integral mechanical force on the earth, however, how gravity contributes to the maintenance of skin function and how microgravity in space affects the wound healing are poorly understood. Here, using microgravity analogs, we show that simulated microgravity (SMG) inhibits the healing of cutaneous wound and the accumulation of dermal fibroblasts in the wound bed. In vitro, SMG inhibits the migration of human foreskin fibroblast cells (HFF‐1), and decreases the F‐actin polymerization and YAP (yes‐associated protein) activity. The SMG‐inhibited migration can be recovered by activating YAP or F‐actin polymerization using lysophosphatidic acid (LPA) or jasplakinolide (Jasp), suggesting the involvement of F‐actin/YAP signaling pathway in this process. In SMG rats, LPA treatment improves the cutaneous healing with increased dermal fibroblasts in the wound bed. Together, our results demonstrate that SMG attenuates the cutaneous wound healing by inhibiting dermal fibroblast migration, and propose the crucial role of F‐actin/YAP mechano‐transduction in the maintenance of skin homeostasis under normal gravity, and YAP as a possible therapeutic target for the skin care of astronauts in space.

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Gravitational effects on fibroblasts’ function in relation to wound healing

Cited by 8 publications

References 59 publications

Morphological Changes of 3T3 Cells under Simulated Microgravity

Morphological Changes of 3T3 Cells under Simulated Microgravity

Naturally Inspired Tree‐Ring Structured Dressing Provides Sustained Wound Tightening and Accelerates Closure

Simulated microgravity attenuates skin wound healing by inhibiting dermal fibroblast migration via F‐actin/YAP signaling pathway

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