The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis

Abstract Objective Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. Results Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

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The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis

10.21203/rs.3.rs-45953/v2 ◽

2020 ◽

Author(s):

Fiona L Cousins ◽

Johanna K Farley ◽

Rebecca Kerrigan ◽

Shayanti Mukherjee ◽

Saeedeh Darzi ◽

...

Keyword(s):

Epithelial Cells ◽

Mouse Model ◽

Peritoneal Cavity ◽

Matched Control ◽

Painful Condition ◽

Hedgehog Signalling ◽

Retrograde Menstruation ◽

Proliferation And Apoptosis ◽

Endometrial Epithelial Cells

Abstract Objective: Endometriosis is a common and painful condition characterized by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of by endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy.Results: Treatment with 5E1, reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

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The Effects of Hedgehog Ligand Neutralising Antibody 5E1 in a Mouse Model of Endometriosis

10.21203/rs.3.rs-45953/v1 ◽

2020 ◽

Author(s):

Fiona Lyndsay Cousins ◽

Johanna K Farley ◽

Rebecca Kerrigan ◽

Shayanti Mukherjee ◽

Saeedeh Darzi ◽

...

Keyword(s):

Epithelial Cells ◽

Mouse Model ◽

Peritoneal Cavity ◽

Painful Condition ◽

Hedgehog Signalling ◽

Endometrial Epithelial Cells

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Role of Estrogen Receptor Signaling Required for Endometriosis-Like Lesion Establishment in a Mouse Model

Endocrinology ◽

10.1210/en.2012-1294 ◽

2012 ◽

Vol 153 (8) ◽

pp. 3960-3971 ◽

Cited By ~ 64

Author(s):

Katherine A. Burns ◽

Karina F. Rodriguez ◽

Sylvia C. Hewitt ◽

Kyathanahalli S. Janardhan ◽

Steven L. Young ◽

...

Keyword(s):

Estrogen Receptor ◽

Mouse Model ◽

Peritoneal Cavity ◽

Critical Role ◽

Receptor Expression ◽

Wild Type ◽

Immunocompetent Mouse ◽

Estradiol Treatment ◽

Estrogen Receptor Signaling

Endometriosis results from ectopic invasion of endometrial tissue within the peritoneal cavity. Aberrant levels of the estrogen receptor (ER), ERα and ERβ, and higher incidence of autoimmune disorders are observed in women with endometriosis. An immunocompetent mouse model of endometriosis was used in which minced uterine tissue from a donor was dispersed into the peritoneal cavity of a recipient. Wild-type (WT), ERα-knockout (αERKO), and βERKO mice were donors or recipients to investigate the roles of ERα, ERβ, and estradiol-mediated signaling on endometriosis-like disease. Mice were treated with vehicle or estradiol, and resulting location, number, and size of endometriosis-like lesions were assessed. In comparison with WT lesions in WT hosts, αERKO lesions in WT hosts were smaller and fewer in number. The effect of ER status and estradiol treatment on nuclear receptor status, proliferation, organization, and inflammation within lesions were examined. αERKO lesions in WT hosts did not form distal to the incision site, respond to estradiol, or proliferate but did have increased inflammation. WT lesions in αERKO hosts did respond to estradiol, proliferate, and show decreased inflammation with treatment, but surprisingly, progesterone receptor expression and localization remained unchanged. Only minor differences were observed between WT lesions in βERKO hosts and βERKO lesions in WT hosts, demonstrating the estradiol-mediated signaling responses are predominately through ERα. In sum, these results suggest ER in both endometriosis-like lesions and their environment influence lesion characteristics, and understanding these interactions may play a critical role in elucidating this enigmatic disease.

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Dissecting the Role of Curcumin in Tumour Growth and Angiogenesis in Mouse Model of Human Breast Cancer

BioMed Research International ◽

10.1155/2015/878134 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 20

Author(s):

Sabrina Bimonte ◽

Antonio Barbieri ◽

Giuseppe Palma ◽

Domenica Rea ◽

Antonio Luciano ◽

...

Keyword(s):

Breast Cancer ◽

Mouse Model ◽

Human Breast Cancer ◽

Cancer Cell Line ◽

Human Breast ◽

Proliferation And Apoptosis ◽

Natural Agent

Breast cancer is considered the most common cancer for women worldwide and it is now the second leading cause of cancer-related deaths among females in the world. Since breast cancer is highly resistant to chemotherapy, alternative anticancer strategies have been developed. In particular, many studies have demonstrated that curcumin, a derivative of turmeric, can be used as natural agent in treatment of some types of cancer by playing antiproliferative and antioxidant effects. In our study, we assessed the antitumor activities of curcumin in ER-negative human breast cancer cell line resistant to chemotherapy, MDA.MB231 byin vitroandin vivoexperiments.In vitrodata allowed us to demonstrate that curcumin played a role in regulation of proliferation and apoptosis in MDA.MB231 cells.In vivo, by generation of mouse model of breast cancer, we showed that treatment of curcumin inhibited tumor growth and angiogenesis. Specifically, we showed that curcumin is able to deregulate the expression of cyclin D1, PECAM-1, and p65, which are regulated by NF-κB. Our data demonstrated that curcumin could be used as an adjuvant agent to chemotherapy in treatment of triple negative breast cancer.

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LincRNA-Cox2 targeting miR-150 regulating the proliferation and apoptosis of chondrocytes in osteoarthritis

10.21203/rs.3.rs-23016/v1 ◽

2020 ◽

Author(s):

Meng Jiang ◽

Kai Xu ◽

Huafeng Ren ◽

Mingmin Wang ◽

Ximin Hou ◽

...

Keyword(s):

Cell Proliferation ◽

Mouse Model ◽

Western Blot ◽

Annexin V ◽

Cartilage Degradation ◽

Protective Role ◽

Joint Disease ◽

Protein Levels ◽

Proliferation And Apoptosis

Abstract Background: Osteoarthritis (OA) is a joint disease characterized by progressive cartilage degradation and inflammation, but the detailed pathogenesis of OA is still unclear. Here, we aimed to investigate the role of LincRNA-Cox2 in OA progression and the potential mechanism.Methods: OA mouse model and IL-1β-induced injury of mouse chondrocytes were conducted. Si-Cox2 was transfected into chondrocytes for elucidating the effect of LincRNA-Cox2 on OA. qR-TPCR was used to detect the expression of LincRNA-Cox2 and miR-150. Cell proliferation and apoptosis were analyzed by MTT assay and Annexin V/PI stain respectively. Western blot was used to evaluate the protein levels in chondrocytes.Results: High levels of LincRNA-Cox2 were observed in both cartilage tissues of OA and IL-1β-treated chondrocytes. Knockdown of LincRNA-Cox2 promoted the proliferation and inhibited apoptosis of chondrocytes. Mechanically, LincRNA-Cox2 directly target to miR-150, acting as a ceRNA, and the effect of si-Cox2 on proliferation and apoptosis in chondrocytes was reversed by miR-150 inhibitor. Moreover, LincRNA-Cox2 had ability to activate wnt/β-catenin pathway to regulate chondrocytes proliferation and apoptosis.Conclusion: Silencing LincRNA-Cox2 plays a protective role in OA by enhancing the proliferation and suppressing apoptosis of chondrocytes, which was related with increase of miR-150 and activation of Wnt/β-catenin pathway.

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circPTPN12/miR-21–5 p/∆Np63α pathway contributes to human endometrial fibrosis

eLife ◽

10.7554/elife.65735 ◽

2021 ◽

Vol 10 ◽

Author(s):

Minmin Song ◽

Guangfeng Zhao ◽

Haixiang Sun ◽

Simin Yao ◽

Zhenhua Zhou ◽

...

Keyword(s):

Epithelial Cells ◽

Mouse Model ◽

Epithelial Mesenchymal Transition ◽

Circular Rnas ◽

Mesenchymal Transition ◽

Organ Fibrosis ◽

Endometrial Epithelial Cells ◽

Expression And Activity ◽

Uterine Infertility

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21–5 p to inhibit miR-21–5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC–EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC–EMT and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

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