Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model

Zhao, Hong; Li, Lin; Coon, John S.; Chatterton, Robert T.; Brooks, David; Jiang, Erhui; Liu, Li; Xu, Xia; Dong, Zhiyong; DeMayo, Francesco J.; Stulberg, Jonah J.; Tourtellotte, Warren G.; Bulun, Serdar E.

doi:10.1073/pnas.1807765115

Cited by 28 publications

(42 citation statements)

References 87 publications

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“…Inguinal hernia is a multifactorial disease caused by endogenous factors including age, gender, anatomic variations, and inheritance as well as exogenous factors such as smoking, comorbidity, and outcomes from surgery [14]. Recently, we found that the conversion of testosterone to estradiol by the aromatase enzyme in lower abdominal muscle tissue in a humanized aromatase transgenic mouse model activates pathways for fibroblast proliferation and fibrosis, leading to intense lower abdominal muscle fibrosis, muscle atrophy, and inguinal hernia; fortunately, an aromatase inhibitor entirely prevents this phenotype [49]. In the present study, we explored the inherited aspects of inguinal hernia formation via data mining of inguinal hernia-causative genes exported from the OMIM database.…”

Section: Discussionmentioning

confidence: 98%

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A network analysis revealed the essential and common downstream proteins related to inguinal hernia

Mao

Chen

et al. 2020

PLoS ONE

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Although more than 1 in 4 men develop symptomatic inguinal hernia during their lifetime, the molecular mechanism behind inguinal hernia remains unknown. Here, we explored the protein-protein interaction network built on known inguinal hernia-causative genes to identify essential and common downstream proteins for inguinal hernia formation. We discovered that PIK3R1, PTPN11, TGFBR1, CDC42, SOS1, and KRAS were the most essential inguinal hernia-causative proteins and UBC, GRB2, CTNNB1, HSP90AA1, CBL, PLCG1, and CRK were listed as the most commonly-involved downstream proteins. In addition, the transmembrane receptor protein tyrosine kinase signaling pathway was the most frequently found inguinal hernia-related pathway. Our in silico approach was able to uncover a novel molecular mechanism underlying inguinal hernia formation by identifying inguinal herniarelated essential proteins and potential common downstream proteins of inguinal herniacausative proteins. OPEN ACCESSCitation: Mao Y, Chen L, Li J, Shangguan AJ, Kujawa S, Zhao H (2020) A network analysis revealed the essential and common downstream proteins related to inguinal hernia. PLoS ONE 15 (1): e0226885. https://doi.org/10.

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Section: Discussionmentioning

confidence: 98%

“…Inguinal hernia formation is associated with increased lower abdominal muscle tissue fibrosis and muscle atrophy [49]. The exact role of these essential and common downstream proteins and the related signaling pathway in fibroblasts and myocytes of lower abdominal muscle tissue is unknown.…”

Section: Discussionmentioning

confidence: 99%

A network analysis revealed the essential and common downstream proteins related to inguinal hernia

Mao

Chen

et al. 2020

PLoS ONE

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“…As early as 1960, Hazary and Gardner reported that male mice given estrogen for prolonged periods developed inguino-scrotal hernias (66). A very recent study by Zhao et al has also revealed that the shift from androgen to estrogen causes inguinal hernia in male mice, and this effect could be entirely prevented by an aromatase inhibitor (67). Tamoxifen is a commonly used selective estrogen receptor modulator that has been used for hormonal treatment of breast cancer for a long time now (68, 69).…”

Section: Discussionmentioning

confidence: 99%

Hernia and Cancer: The Points Where the Roads Intersect

Kulaçoğlu¹,

Köckerling

2019

Front. Surg.

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Introduction: This review aimed to present common points, intersections, and potential interactions or mutual effects for hernia and cancer. Besides direct relationships, indirect connections, and possible involvements were searched. Materials and Methods: A literature search of PubMed database was performed in July 2018 as well as a search of relevant journals and reference lists. The total number of screened articles was 1,422. Some articles were found in multiple different searches. A last PubMed search was performed during manuscript writing in December 2018 to update the knowledge. Eventually 427 articles with full text were evaluated, and 264 included, in this review. Results: There is no real evidence for a possible common etiology for abdominal wall hernias and any cancer type. The two different diseases had been found to have some common points in the studies on genes, integrins, and biomarkers, however, to date no meaningful relationship has been identified between these points. There is also some, albeit rather conflicting, evidence for inguinal hernia being a possible risk factor for testicular cancer. Neoadjuvant or adjuvant therapeutic modalities like chemotherapy and radiotherapy may cause postoperative herniation with their adverse effects on tissue repair. Certain specific substances like bevacizumab may cause more serious complications and interfere with hernia repair. There are only two articles in PubMed directly related to the topic of “hernia and cancer.” In one of these the authors claimed that there was no association between cancer development and hernia repair with mesh. The other article reported two cases of squamous-cell carcinoma developed secondary to longstanding mesh infections. Conclusion: As expected, the relationship between abdominal wall hernias and cancer is weak. Hernia repair with mesh does not cause cancer, there is only one case report on cancer development following a longstanding prosthetic material infections. However, there are some intersection points between these two disease groups which are worthy of research in the future.

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“…Hong Zhao et al found a link between hormones and hernias accidentally while experimenting on a murine model for breast cancer research. 1 They had created humanized transgenic mice by genetically modifying them to carry the human gene for aromatase. Aromatase is a key enzyme for conversion of testosterone into oestrogen.…”

Section: Review Of Literaturementioning

confidence: 99%

“…Hence a corollary which follows this observation is that therapy with aromatase inhibitors could possibly prevent the occurrence of a hernia or prevent recurrence. 1 Body mass index (BMI) has been linked to the aetiology of inguinal hernia. 2,3 However the association at times seems to be confusing.…”

Section: Review Of Literaturementioning

confidence: 99%

Enigmatic aetiology of inguinal hernia

Vagholkar¹,

Vagholkar²

2019

Int Surg J

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The aetiology of inguinal hernia continues to be a topic for debate. A wide range of hypothesis have been postulated over a period of time. These are based on genetic factors, tissue configuration, biochemical enzymatic activity and anatomical structural weaknesses. None of these except the anatomical basis has helped in the evolution of hernia surgery. The article reviews the contemporary hypothesis postulated for the aetiology of inguinal hernias.

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Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model

Cited by 28 publications

References 87 publications

A network analysis revealed the essential and common downstream proteins related to inguinal hernia

A network analysis revealed the essential and common downstream proteins related to inguinal hernia

Hernia and Cancer: The Points Where the Roads Intersect

Enigmatic aetiology of inguinal hernia

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