UFMylation is associated with LPS‐induced inflammatory response in goat endometrial epithelial cells

Xiao, Jinbang; Liu, Shouqin; Yu, Tong; Zhang, Ruixue; Guo, Xinyan; Jia, Yanni; Shang, Chunmei; Wang, Aihua; Jin, Yaping; Lin, Peng

doi:10.1111/rda.13832

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…Interestingly, overexpression of UFL1 could alleviate ER stress and reduce cisplatin-induced damage to the ovary, in the end augmenting follicle number and restoring estrogen secreted by GCs to some extent. Similarly, UFM1 silencing was found to enhance ER stress but not oxidative stress-induced GC apoptosis during goat follicular development and atresia, suggesting a conserved role of UFMylation in the prevention of cell death related to the ER in ovaries ( 97 ).…”

Section: Ufmylation In Endocrine Glandsmentioning

confidence: 90%

Emerging role of UFMylation in secretory cells involved in the endocrine system by maintaining ER proteostasis

et al. 2023

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Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like molecule (UBL) discovered almost two decades ago, but our knowledge about the cellular and molecular mechanisms of this novel protein post-translational modification is still very fragmentary. In this review, we first summarize the core enzymes and factors involved in the UFMylation cascade, which, similar to ubiquitin, is consecutively catalyzed by UFM1-activating enzyme 5 (UBA5), UFM1-conjugating enzyme 1 (UFC1) and UFM1-specific ligase 1 (UFL1). Inspired by the substantial implications of UFM1 machinery in the secretory pathway, we next concentrate on the puzzling role of UFMylation in maintaining ER protein homeostasis, intending to illustrate the underlying mechanisms and future perspectives. At last, given a robust ER network is a hallmark of healthy endocrine secretory cells, we emphasize the function of UFM1 modification in physiology and pathology in the context of endocrine glands pancreas and female ovaries, aiming to provide precise insight into other internal glands of the endocrine system.

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Section: Ufmylation In Endocrine Glandsmentioning

confidence: 90%

Emerging role of UFMylation in secretory cells involved in the endocrine system by maintaining ER proteostasis

et al. 2023

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“…In domestic animals, ISG15 has been shown to be expressed in epithelial and stromal cells of the endometrium in cattle, horses, and sheep [ 32 , 33 , 34 ] and is located in the nucleus, nuclear stroma, cytoplasm, and organelles of bovine subcellular structures [ 32 ]. In the present study, LPS was used to induce an inflammatory response in gEECs to successfully construct an in vitro model of goat endometritis, as has been previously reported in earlier studies [ 26 ]. Here, we found that ISG15 was mostly localized in the cytoplasm, with low levels of expression in the nucleus, essentially consistent with previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…At the end of the culture, the cells were collected for mRNA and protein experiments. The concentration of LPS was determined by previous studies in our laboratory and has been proved to cause an obvious inflammatory response of gEECs [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

ISGylation Inhibits an LPS-Induced Inflammatory Response via the TLR4/NF-κB Signaling Pathway in Goat Endometrial Epithelial Cells

Xiao

Zhang

et al. 2021

Animals

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Endometritis is a common and important reproductive disease of domestic animals. The principal factors responsible for the disease are infection with Gram-negative bacteria, the release of Lipopolysaccharides (LPS) and activation of the TLR4/NF-κB signaling pathway. However, we do not fully understand the interaction between endometrial immunity and bacterial infection in the disease etiology. The ubiquitin-like protein ISG15 can regulate the TLR4/NF-κB signaling pathway via the ISGylation modification system, modulating the inflammatory response. In the present study, we found that ISG15 protein was expressed mainly in the cytoplasm of goat endometrial epithelial cells (gEECs) and that the expression of key genes and proteins of ISGylation increased in LPS-induced gEECs. Overexpression and silencing of the ISG15 gene demonstrated that ISGylation inhibited an LPS-induced inflammatory response via the TLR4/NF-κB signaling pathway in gEECs. Here, we provide the experimental basis for further exploration of the role of the ISGylation modification system in the inflammatory response of endometrium and a potential method for the treatment of endometritis.

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“…Recently researches have confirmed that UFL1 plays a crucial role in some biological process such as cell proliferation, differentiation and embryonic development (25)(26)(27)(28), but the function of UFL1 in POF has not been explored. In this study, we firstly revealed that UFL1 is expressed in GCs, oocytes and stromal cells in ovarian tissues.…”

Section: Discussionmentioning

confidence: 99%

UFL1 Relieves Cisplatin-Induced Premature Ovarian Failure by Reducing Endoplasmic Reticulum Stress in Granulosa Cells

Tang

Dong

Fang

et al. 2021

Preprint

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BackgroundUbiquitin-like modifier 1 ligating enzyme 1 (UFL1), the ligase of the Ufmylation system, has recently been reported to be involved in apoptosis and endoplasmic reticulum stress (ER stress) in a variety of diseases. Premature ovarian failure (POF) is a gynecological disease that severely reduces the fertility of women, especially in female cancer patients receiving chemotherapy drugs. Whether UFL1 is involved in the protection from chemotherapy-induced POF and its mechanism remains unclear. MethodsIn this study, we examined the function of UFL1 in ovarian dysfunction and granular cells (GCs) apoptosis induced by cisplatin through histological examination and cell viability analysis. We used western blot, quantitative real-time PCR (qPCR) and immunofluorescence (IF) to detect the expression of UFL1 and the level of ER stress specific makers. Enzyme-Linked Immunosorbent Assays were used to detect the level of Follicle-Stimulating Hormone (FSH) and Estrogen (E2) in ovaries and GCs. In addition, we knocked down or overexpressed UFL1 in ovaries or GCs through infected with lentiviral particle suspensions, respectively. ResultsOur data showed that the expression of UFL1 was reduced in POF model ovaries and was accompanied by the occurrence of ER stress. In vitro, cisplatin induced a stressful increase of UFL1 expression in GCs, and enhanced ER stress, which was aggravated by UFL1 knockdown and alleviated by UFL1 overexpression. Furthermore, the data showed that UFL1 knockdown resulted in a decrease of ovarian follicles number, an increase of atretic follicles, and a decreased expression of AMH and FSHR. Conversely, overexpression of UFL1 reduced the damage of cisplatin to the ovary in vitro. ConclusionsOur research proved that UFL1 regulates cisplatin-induced ER stress and apoptosis of GCs, and participates in the protection from cisplatin-induced POF, providing a potential therapeutic target for clinical prevention of chemotherapeutic drug-induced POF.

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UFMylation is associated with LPS‐induced inflammatory response in goat endometrial epithelial cells

Cited by 9 publications

References 33 publications

Emerging role of UFMylation in secretory cells involved in the endocrine system by maintaining ER proteostasis

Emerging role of UFMylation in secretory cells involved in the endocrine system by maintaining ER proteostasis

ISGylation Inhibits an LPS-Induced Inflammatory Response via the TLR4/NF-κB Signaling Pathway in Goat Endometrial Epithelial Cells

UFL1 Relieves Cisplatin-Induced Premature Ovarian Failure by Reducing Endoplasmic Reticulum Stress in Granulosa Cells

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