Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis

Dewanto, Agung, Dudas, Jozsef, Glueckert, Rudolf, Mechsner, Sylvia, Schrott-Fischer, Anneliese, Wildt, Ludwig, Seeber, Beata
2016 · doi:10.17169/refubium-19555 · W6962552061
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This study compared neurotrophin receptor expression in peritoneal and deep infiltrating endometriosis, finding higher TrkB and p75 immunostaining in the stroma of deep infiltrating lesions than in peritoneal lesions.

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This immunohistochemical study examined the expression and localization of neurotrophins and their receptors, specifically TrkB and p75, in peritoneal endometriosis and deep infiltrating endometriosis tissues. The researchers analyzed twenty peritoneal lesions and twenty-two deep infiltrating lesions to compare cell staining percentages for BDNF, NGF, TrkA, TrkB, p75, and nerve fiber markers. Results indicated that while BDNF levels were similarly high in both conditions, TrkB and p75 receptors were significantly more expressed in the stroma of deep infiltrating lesions compared to peritoneal ones. Although overall nerve density did not differ between general groups, bowel-related deep infiltrating lesions showed significantly higher nerve density than peritoneal or non-bowel deep infiltrating lesions. This paper is centrally about endometriosis — specifically comparing receptor expression profiles in peritoneal versus deep infiltrating disease subtypes.

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Abstract

Background The roles of the neurotrophins NGF (Neurotrophic growth factor) and BDNF (brain-derived neurotrophic factor) in neuronal growth and development are already known. Meanwhile, the neurotrophin receptors TrkA (tropomyosin related kinase A), TrkB, and p75 are important for determining the fate of cells. In endometriosis, this complex system has not been fully elucidated yet. The aim of this study was to evaluate the expression and location of these neurotrophins and their receptors in peritoneal (PE) and deep infiltrating endometriotic (DIE) tissues and to measure and compare the density of nerve fibers in the disease subtypes. Methods PE lesions (n = 20) and DIE lesions (n = 22) were immunostained and analyzed on serial slides with anti-BDNF, −NGF, −TrkA, −TrkB, −p75,-protein gene product 9.5 (PGP9.5, intact nerve fibers) and -tyrosine hydroxylase (TH, sympathetic nerve fibers) antibodies. Result There was an equally high percentage (greater than 75 %) of BDNF-positive immunostaining cells in both PE and DIE. TrkB (major BDNF receptor) and p75 showed a higher percentage of immunostaining cells in DIE compared to in PE in stroma only (p
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Abstract

Background The roles of the neurotrophins NGF (Neurotrophic growth factor) and BDNF (brain-derived neurotrophic factor) in neuronal growth and development are already known. Meanwhile, the neurotrophin receptors TrkA (tropomyosin related kinase A), TrkB, and p75 are important for determining the fate of cells. In endometriosis, this complex system has not been fully elucidated yet. The aim of this study was to evaluate the expression and location of these neurotrophins and their receptors in peritoneal (PE) and deep infiltrating endometriotic (DIE) tissues and to measure and compare the density of nerve fibers in the disease subtypes. Methods PE lesions (n = 20) and DIE lesions (n = 22) were immunostained and analyzed on serial slides with anti-BDNF, −NGF, −TrkA, −TrkB, −p75,-protein gene product 9.5 (PGP9.5, intact nerve fibers) and -tyrosine hydroxylase (TH, sympathetic nerve fibers) antibodies. Result There was an equally high percentage (greater than 75 %) of BDNF-positive immunostaining cells in both PE and DIE. TrkB (major BDNF receptor) and p75 showed a higher percentage of immunostaining cells in DIE compared to in PE in stroma only (p < 0.014, p < 0.027, respectively). Both gland and stroma of DIE lesions had a lower percentage of NGF-positive immunostaining cells compared to those in PE lesions (p < 0.01 and p < 0.01, respectively), but there was no significant reduction in immunostaining of TrkA in DIE lesions. There was no difference in the mean density of nerve fibers stained with PGP9.5 between PE (26.27 ± 17.32) and DIE (28.19 ± 33.15, p = 0.8). When we performed sub-group analysis, the density of nerves was significantly higher in the bowel DIE (mean 57.33 ± 43.9) than in PE (mean 26.27 ± 17.32, p < 0.01) and non-bowel DIE (mean 14.6. ± 8.6 p < 0.002). Conclusions While the neurotrophin BDNF is equally present in PE and DIE, its receptors TrkB and p75 are more highly expressed in DIE and may have a potential role in the pathophysiology of DIE, especially in promotion of cell growth. BDNF has a stronger binding affinity than NGF to the p75 receptor, likely inducing sympathetic nerve axonal pruning in DIE, resulting in the lower nerve fiber density seen. Identifier: Language: English

Keywords

Neurotrophins BDNF Endometriosis Immunohistochemistry BDNF Endometriosis Immunohistochemistry DDC-Classification: 610 Medizin und Gesundheit Publication Type: Wissenschaftlicher Artikel Also published in: Reproductive Biology and Endocrinology. - 14 (2016), Artikel Nr. 43 URL of the Original Publication: DOI of the Original Publication: Department/institution: Charité - Universitätsmedizin Berlin Comments: Der Artikel wurde in einer Open-Access-Zeitschrift publiziert. art_3A10.1186_2Fs12958-016-0178-5.pdf Size: 3.272MB Format: PDF Checksum (MD5): 2b66827f25792d5c73ced6f143ad0a79

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