Estrogen Effects on Wound Healing

Horng, Huann Cheng; Chang, Wen Yin; Yeh, Chien-Yuh; Huang, Ben; Chang, Chia Pei; Chen, Yi Jen; Tsui, Kuan Hao; Wang, Peng Hui

doi:10.3390/ijms18112325

Cited by 134 publications

(96 citation statements)

References 104 publications

(241 reference statements)

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“…In particular, the roles of platelets in the development of endometriosis has been demonstrated only recently 23 , despite the disease is characterized conspicuously by cyclic bleeding 55 . Indeed, estrogen is very important to wound healing 27,28 and so is ERβ 37,38 in wound healing, another similarity that cannot be dismissed as just a pure coincidence. In essence, this study shows that, as wounds undergoing ReTIAR, platelets also participate in the increased local production of estrogens through various ways.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings give more credence to the notion that endometriotic lesions are wounds undergoing ReTIAR. Indeed, peripheral tissues produce estrogens 71 , and estrogens play a vital role in wound healing 27,28 . While normal endometrial stromal cells only produce negligible levels of estrogens 41 likely due to a silenced aromatase because of hypermethylation 41,42 , endometriotic stromal cells, in contrast, do produce a much higher level of estrogens, www.nature.com/scientificreports www.nature.com/scientificreports/ due to demethylated aromatase 42 , and overexpression of StAR, HSD3B2 and HSD17B1 12,43,45,47 .…”

Section: Discussionmentioning

confidence: 99%

“…In wound healing, estrogen has been well documented to be actively involved 27,28 . Numerous studies have shown that estrogen is important to wound healing, and its deficiency delays or impairs wound healing [29][30][31][32][33] .…”

mentioning

confidence: 99%

“…Numerous studies have shown that estrogen is important to wound healing, and its deficiency delays or impairs wound healing [29][30][31][32][33] . In fact, estrogen is found to be involved in all phases of wound healing 27 . One gene expression profiling study of wound tissues from young and elder men found that among genes that were differentially expressed, 78% of them being estrogen-regulated and only 3% being age-related 34 , suggesting that estrogen is more important than intrinsic aging in wound healing.…”

mentioning

confidence: 99%

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Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells

Liu

Zhang

et al. 2020

Sci Rep

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Endometriosis is estrogen-dependent disorder. Two theories provide the explanations for the increased estrogen production. One is the feed-forward loop model linking inflammation and estrogen production. The more recent model evokes the tissue hypoxia resulting from endometrial debris detached and then regurgitated to the peritoneal cavity. Both models tacitly assume that everything occurs within the endometriotic stromal cells, seemingly without the need for exogenous factors. This study was undertaken to investigate as whether platelets may be responsible for local estrogen overproduction. We employed in vitro experimentation that evaluated the 17β-estradiol (e 2) levels in endometriotic stromal cells treated with activated platelets, and the genes and protein expression levels of StAR, HSD3B2, aromatase, and HSD17B1, as well as their upstream genes/proteins such as nf-κB, TGF-β1, HIF-1α, SF-1 and phosphorylated CREB. In addition, we conducted 2 animal experimentations using platelet depletion/infusion and also neutralization of NF-κB and tGf-β1, followed by immunohistochemistry analysis of involved in StAR, HSD3B2, aromatase, and HSD17B1, as well as SF-1 and p-CREB. We found that treatment of endometriotic stromal cells by activated platelets increase the e 2 production by 4.5 fold, and concomitant with increased gene and protein expression of StAR, HSD3B2, aromatase, and HSD17B1, the four genes/enzymes important to estrogen synthesis, along with their upstream genes HIF-1α, SF-1 and phosphorylated CREB. Moreover, platelets activate these genes through the activation of NF-κB and/or TGF-β1, and antagonism of either signaling pathway can abolish the induction of the 4 genes and thus increased estrogen production. The two animal experimentations confirmed these changes. Thus, platelets increase the E 2 production in endometriotic stromal cells through upregulation of StAR, HSD3B2, aromatase, and HSD17B1 via the activation of NF-κB and/or TGF-β1. These findings provide a yet another compelling piece of evidence that endometriotic lesions are indeed wounds undergoing repeated tissue injury and repair. They strongly indicate that non-hormonal therapeutics for endometriosis is theoretically viable, with antiplatelet therapy being one promising avenue. Endometriosis, defined as the deposition and growth of endometrium-like tissues outside the uterine cavity, is a common disorder affecting about 6-10% of women of reproductive age 1. As a major contributor to pelvic pain and infertility 2 impacting negatively on women's quality of life 3 , a source of anxiety and depression 4 and a leading cause of gynecological hospitalization in the United States 5 and likely in many other parts of the world, endometriosis is frequently viewed as an enigmatic disease due to its elusive pathogenesis and pathophysiology 6,7. Consequently, its effective treatment remains a challenge 2,8. Endometriosis has been viewed as a ultimate hormonal disease 9 , featuring estrogen-dependent growth and maintenance of ectopic endometrium as well as ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells

Liu

Zhang

et al. 2020

Sci Rep

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“…Some studies have shown that sex [41] and the levels of sex hormones have an impact on woundhealing potential. Oestrogen is thought to stimulate healing, and testosterone to induce it [47].…”

Section: Factors That Delay Wound Healing and Influence Scar Outcomementioning

confidence: 99%

Studying the healing and long-term outcomes of two partial thickness wound models using different wound dressings

Karlsson

2019

Linköping University Medical Dissertations

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Background: Safe and effective wound dressing treatments are important for proper wound healing. Such procedures therefore need to be evidence-based regarding the most important outcome measures such as healing time, less discomfort for the patient, duration of hospital care and, importantly, less scarring. As the relation between longer healing times and more severe scarring is known, it is important to find dressing treatments that reduces such complications by providing fast and proper wound healing. In this thesis, four established wound dressing treatments (hydrofibre covered with film; porcine xenografts and polyurethane foam, with and without silver), were evaluated for two types of acute, partial thickness wounds: split thickness skin graft (STSG) donor sites and partial thickness burn wounds in two randomised, controlled clinical trials (RCT) with longterm scar follow ups. The relations between factors thought to influence wound healing and scarring as sex, infection, wound extent and depth, healing time and skin grafting were also investigated in these two wound models. Methods: Data from these trials were collected on sex, infection rates, wound depth and extent, need of skin grafting, healing times and scarring frequency together with demographic data. Scars were evaluated at 8 years in Study II and III and at 6 and 12 months after injury in Study V.

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Photobiomodulation in diabetic wound healing: A review of red and near‐infrared wavelength applications

Oyebode

Houreld

Abrahamse

2021

Cell Biochemistry & Function

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The development of a painless, non‐invasive, and faster way to diabetic wound healing is at the forefront of research. The complexity associated with diabetic wounds makes it a cause for concern amongst diabetic patients and the world at large. Irradiation of cells generates a photobiomodulatory response on cells and tissues, directly causing alteration of cellular processes and inducing diabetic wound repair. Photobiomodulation therapy (PBMT) using red and near‐infrared (NIR) wavelengths is being considered as a promising technique for speeding up the rate of diabetic wound healing, eradication of pain and reduction of inflammation through the alteration of diverse cellular and molecular processes. This review presents the extent to which the potential of red and NIR wavelengths have been harnessed in PBMT for diabetic wound healing. Important research challenges and gaps are identified and discussed, and future directions mapped out. This review thus provides useful insights and strategies into improvement of PBMT, including its acceptance within the global medical research community.

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Estrogen Effects on Wound Healing

Cited by 134 publications

References 104 publications

Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells

Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells

Studying the healing and long-term outcomes of two partial thickness wound models using different wound dressings

Photobiomodulation in diabetic wound healing: A review of red and near‐infrared wavelength applications

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