Necrostatin‐1, RIP1/RIP3 inhibitor, relieves transforming growth factor β‐induced wound‐healing process in formation of hypertrophic scars

2020 ◽  
Author(s):  
Pei‐Ting Lin ◽  
Xiao‐Dong Xue ◽  
Zhong‐Dong Zhao ◽  
Jun‐Yang Lu ◽  
Pei‐Lin Xie
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Wound Healing Process ◽  
Hypertrophic Scars

Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin

2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.

Temporal Effects of Different Vehicles on Wound Healing Potentials of Quercetin: Biochemical, Molecular, and Histopathological Approaches

2020 ◽  
pp. 153473462097758
Author(s):  
Vinay Kant ◽  
Manish Kumar ◽  
Babu Lal Jangir ◽  
Vinod Kumar
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Corn Oil ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Wound Healing Process ◽  
Protein Levels ◽  
Ointment Base ◽  
Factor Α

Development of novel drugs or formulations to accelerate the wound healing process is the need of current era. Quercetin (Q), a bioflavonoid, at 0.3% concentration has showed some wound healing potential in our preliminary studies. The present study was aimed to explore the wound healing potential of 0.3% quercetin formulated in 3 different vehicles, that is, dimethyl sulfoxide (DMSO; 10%), ointment base, and corn oil. Ninety experimentally wounded rats were grouped in 6 groups. The 0.3% quercetin mixed with DMSO, ointment base, and corn oil was topically applied once daily for 21 days on the wounds of groups 2, 4, and 6, respectively. DMSO, ointment base, and corn oil alone was applied similarly in groups 1, 3, and 5, respectively. Gross evaluation and wound contraction results revealed accelerated wound closure in all quercetin-treated groups. The mRNA expressions of vascular endothelial growth factor, transforming growth factor-β1, and interluekin-10 were markedly upregulated in healing tissues of quercetin-treated groups. Tumor necrosis factor-α mRNA expression and protein levels were lowered by quercetin treatment. Quercetin-treated groups also showed increased activities of SOD (superoxide dismutase) and catalase, and levels of total thiols in wound tissues on day 7. Levels of superoxide anion radicals and malondialdehyde were markedly lower in quercetin-treated groups. Histologically, wound sections of quercetin-treated groups showed early dominance of fibroblasts, increased blood vessels, marked collagen deposition, and regenerated epithelial layer. The significant effects were more pronounced in ointment + Q group among all the quercetin-treated groups. In conclusion, 0.3% quercetin mixed in ointment base produced the fastest and better wound healing in rats.

Transforming growth factor-? isoforms differently stimulate pro?2 (I) collagen gene expression during wound healing process in transgenic mice

2002 ◽  
Vol 190 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Takuro Kinbara ◽  
Fumiaki Shirasaki ◽  
Shigeru Kawara ◽  
Yutaka Inagaki ◽  
Benoit de Crombrugghe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Wound Healing Process ◽  
Collagen Gene ◽  
Collagen Gene Expression

scholarly journals The extracellular matrix: an active or passive player in fibrosis?

2011 ◽  
Vol 301 (6) ◽  
pp. G950-G955 ◽  
Author(s):  
Thomas N. Wight ◽  
Susan Potter-Perigo
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Cytokine Signaling ◽  
Wound Healing Process ◽  
Inflammatory Stimuli ◽  
Specialized Form ◽  
Excessive Accumulation

Fibrosis is characterized by excessive accumulation of collagen and other extracellular matrix (ECM) components, and this process has been likened to aberrant wound healing. The early phases of wound healing involve the formation of a provisional ECM containing fibrin, fibrinogen, and fibronectin. Fibroblasts occupy this matrix and proliferate in response to activators elaborated by leukocytes that have migrated into the wound and are retained by the ECM. This coincides with the appearance of the myofibroblast, a specialized form of fibroblast whose differentiation is primarily driven by cytokines, such as transforming growth factor-β (TGF-β), and by mechanical tension. When these signals are reduced, as when TGF-β secretion is reduced, or as in scar shrinkage, myofibroblasts undergo apoptosis, resulting in a collagen-rich, cell-poor scar. Retention of myofibroblasts in fibrosis has been described as the result of imbalanced cytokine signaling, especially with respect to levels of activated TGF-β. ECM components can regulate myofibroblast persistence directly, since this phenotype is dependent on extracellular hyaluronan, tenascin-C, and the fibronectin splice variant containing the “extra domain A,” and also, indirectly, through retention of TGF-β-secreting cells such as eosinophils. Thus the ECM is actively involved in both cellular and extracellular events that lead to fibrosis. Targeting components of the ECM as cells respond to injury and inflammatory stimuli holds promise as a means to avoid development of fibrosis and direct the wound-healing process toward reestablishment of a healthy equilibrium.

scholarly journals Topical Gynura procumbens as a Novel Therapeutic Improves Wound Healing in Diabetic Mice

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1122
Author(s):  
Nutda Sutthammikorn ◽  
Volaluck Supajatura ◽  
Hainan Yue ◽  
Miho Takahashi ◽  
Sunee Chansakaow ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Healing Process ◽  
Unmet Need ◽  
New Drugs ◽  
Wound Healing Process ◽  
Diabetic Mice ◽  
Diabetic Wounds

Nonhealing wounds are major socioeconomic challenges to healthcare systems worldwide. Therefore, there is a substantially unmet need to develop new drugs for wound healing. Gynura procumbens, a herb found in Southeast Asia, may be an effective therapeutic for nonhealing diabetic wounds. The aim of this study was to evaluate the efficacy of G. procumbens on wound healing in the diabetic milieu. G. procumbens extract was obtained using 95% ethanol and its components were determined by thin layer chromatography. Diabetes was induced in mice using streptozotocin. We found that G. procumbens extract contained stigmasterol, kaempferol and quercetin compounds. Topical application of G. procumbens on the wounded skin of diabetic mice accelerated wound healing and induced the expression of angiogenin, epidermal growth factor, fibroblast growth factor, transforming growth factor and vascular endothelial growth factor. Furthermore, G. procumbens promoted in vitro wound healing and enhanced the migration and/or proliferation of human endothelial cells, fibroblasts, keratinocytes and mast cells cultured in diabetic conditions. Finally, G. procumbens promoted vascular formation in the diabetic mice. To the best of our knowledge, this is the first study that evaluates in vivo wound healing activities of G. procumbens and activation of cells involved in wound healing process in diabetic conditions. The findings that G. procumbens accelerates wound healing and activates cells involved in the wound healing process suggest that G. procumbens might be an effective alternative therapeutic option for nonhealing diabetic wounds.

scholarly journals Application of pomegranate (Punica granatum Linn.) fruit extract for accelerating post-tooth extraction wound healing

2018 ◽  
Vol 51 (4) ◽  
pp. 189
Author(s):  
Intan Nirwana
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Treatment Group ◽  
Tooth Extraction ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Punica Granatum ◽  
Control Group ◽  
Wound Healing Process ◽  
Significant Difference

Background: Trauma occurring during tooth extraction can cause complications such as bleeding, infection, fracture and dry socket and constitutes an inflammatory response trigger. Pomegranate (Punica granatum Linn.) extract, which contains large amounts of punicallagin and ellagic acid, possesses various qualities, including; anti-inflammatory, anti-bacterial and anti-oxidant. Pomegranate extract can inhibit proinflammatory cytokine production, while also suppressing inflammation response thereby accelerating wound healing. Purpose: This study aimed to analyze the effect of pomegranate extract application to the tooth extraction wounds of Cavia cobaya (C. cobaya) on the expression of fibroblast growth factor-2 (FGF-2) and transforming growth factor β (TGF-β) on the fourth day of the wound-healing process. Methods: This study used 12 C. cobaya, divided into two groups, namely; control and treatment. The subjects were anesthetized, before their lower left central incisor was extracted and the entire socket filled with CMC-Na 3% in members of the control group and pomegranate extract in those of the treatment group. The twelve C. cobaya were sacrificed on day 4, their lower jaw subsequently being removed and decalcified for approximately 30 days. The mandibula tissue was stained using a immunohistochemical technique. FGF-2 and TGF-β were used to evaluate the healing process in the extracted tooth socket. Differences in the expression of FGF-2 and TGF-β were evaluated statistically by means of a t-test. Results: This study indicated a significant difference between the control and the treatment groups (p<0.05). The treatment group members whose sockets were filled with pomegranate extract showed high FGF-2 and TGF-β expression. Conclusion: This study confirmed that the administration of pomegranate extract to post-extraction tooth wounds of C. cobaya increases the expression of FGF-2 and TGF-β on day 4, thereby accelerating the wound healing process.

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

2020 ◽  
Author(s):  
Sylwia Machcinska ◽  
Marta Kopcewicz ◽  
Joanna Bukowska ◽  
Katarzyna Walendzik ◽  
Barbara Gawronska-Kozak
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Limiting Factor ◽  
Skin Wound Healing ◽  
Collagen Iii

ABSTRACTHypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using Foxn1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. The Foxn1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the Foxn1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of the 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.

Sign in / Sign up

Export Citation Format

Share Document