Disease relevance of INHBE

• Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma [1].
• The comparisons revealed significantly elevated concentrations of activin A in patients with meningitis (P=0.017) [2].
• Activin A concentrations in CSF of patients with various neurological diseases, including meningitis, chronic inflammatory CNS diseases, neurodegenerative diseases, tumors in the CNS, cerebral ischemia, intracerebral/subarachnoid hemorrhages, subdural hemorrhages and epileptic seizures, were compared with age- and sex-matched control patients [2].
• Activin effects on neoplastic proliferation of human pituitary tumors [3].
• Expression and localization of activin subunits and follistatins in tissues from men with high grade prostate cancer [4].

Psychiatry related information on INHBE

• Id proteins: novel targets of activin action, which regulate epidermal homeostasis [5].

High impact information on INHBE

• In the process other factors such as activin and follistatin were serendipitously discovered [6].
• Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses [7].
• The identification of protein factors, such as epimorphin, scatter factor, and activin, that induce epithelial branching and convergent extension-like movements in embryonic tissues are important breakthroughs in our understanding of the role of mesenchyme in epithelial morphogenesis [8].
• Nodal signaling activates a canonical TGFss pathway involving activin receptors, Smad2 transcription factors, and FoxH1 coactivators [9].
• The TGF-beta/activin/BMP superfamily of growth factors signals through heteromeric receptor complexes of type I and type II serine/threonine kinase receptors [10].

Chemical compound and disease context of INHBE

• Activin inhibition of prostate cancer cell growth: selective actions on androgen-responsive LNCaP cells [11].
• Activin acts mitogenically on P19 cells as well as being inhibitory of the differentiation of retinoic acid-treated P19 cells and some neuroblastoma cell lines [12].
• A rapid and robust release of activin A and follistatin occurred in the circulation of patients undergoing abdominal aortic aneurysm repair or carotid endarterectomy at the time of vessel clamping and administration of heparin (5000 IU) [13].
• The present study was conducted to further characterize the effects of activin A in two glucose-responsive insulinoma cell lines, MIN6 and HIT-T15 cells [14].
• This led us to propose that there may be a relationship between hypoxia and activin A, follistatin and prostaglandin (PG) release from the feto-placental unit [15].

Biological context of INHBE

• The effect of activin and FS on cell proliferation was assessed by measuring [3H]thymidine incorporation [1].
• Treatment with activin or FS did not consistently affect cell growth [1].
• Activin-binding affinities and kinetics were comparable between the isoforms and FSTL3, whereas cell-surface binding differed markedly (FST288 > FST303 > FST315 > FSTL3) [16].
• Activin and follistatin (FS) appear to play a role in the development of the skin and its appendages, in the inflammatory process, angiogenesis, and in wound healing [17].
• OBJECTIVE: Activin A, and its binding protein, follistatin (FS), are expressed in the central nervous system (CNS) [2].

Anatomical context of INHBE

• Moreover, when FSTL3, which does not associate with cell membranes, was expressed as a membrane-anchored protein, its endogenous activin inhibitory activity was dramatically increased [16].
• Although there is information on the expression of activin subunits and receptors in fibroblasts and keratinocytes, there are no reports on the regulation of FS expression in these cells [17].
• We conclude that the expression of activin and inhibin subunits, receptors and binding proteins is affected by tumour formation in the adrenal gland and may play a role in tumorigenesis [18].
• Objective The growth and differentiation factors activin and inhibin can affect tumour formation and steroid production in the adrenal cortex [18].
• Activin A concentrations in human cerebrospinal fluid are age-dependent and elevated in meningitis [2].

Associations of INHBE with chemical compounds

• Blood samples were obtained from the patients on day 3-5 of a progesterone-induced or spontaneous cycle and were assayed for LH, FSH, testosterone, 17-hydroxy-progesterone, androstenedione, follistatin, activin A, fasting glucose and insulin [19].
• BACKGROUND: Activin promotes ovarian follicular development, inhibits androgen production and increases FSH and insulin secretion [19].
• Activin A was significantly and independently negatively affected by PCOS (P < 0.003) and FSH (P < 0.03), and positively affected by weight (P < 0.009) and androstenedione (P < 0.02) [19].
• This activin degradation was abolished by heparan sulfate, chloroquine, and several lysosomal enzyme inhibitors [20].
• Moreover, FS-288 stimulated cellular uptake of activin A, whereas chloroquine suppressed lysosomal degradation following internalization, as demonstrated by microscopic autoradiography [20].

Physical interactions of INHBE

• A continuous sequence comprising the N-terminal domain and followed by FS domains 1 and 2 fulfills the minimum structural requirement for activin binding and FS bioactivity [21].
• No effects on ligand binding to follistatin-like module I or II were observed after the binding of activin A to native protein [22].
• Alpha 2-macroglobulin is a binding protein of inhibin and activin [23].
• Cross-linked 125I-labeled inhibin or activin plasma binding protein complexes comigrated with [125I] inhibin or [125I]activin cross-linked to h alpha 2M [23].
• In addition, eleven mutants partially affected activin binding to ALK4 [24].

Enzymatic interactions of INHBE

• Smad2 and Smad3 were phosphorylated in response to activin and accumulated in the nucleus of treated T47D cells [25].

Regulatory relationships of INHBE

• Activin A stimulated total ir-FS production by undifferentiated and partially differentiated GC, but inhibited total ir-FS production by fully differentiated GC [26].
• Crucial role of activin a in tubulogenesis of endothelial cells induced by vascular endothelial growth factor [27].
• Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway [28].
• In the secretion study, activin A secretion at 8-10 weeks was significantly stimulated by IL-1beta and EGF [29].
• Finally we demonstrate that FLRG protein regulates its own activin-induced expression [30].

Other interactions of INHBE

• The effect of activin is most likely mediated through specific receptors as mRNAs encoding several forms of activin receptors, namely ActR-I, ActR-IB, ActR-II and ActR-IIB are found in the preovulatory follicles as well as in cultured granulosa-luteal cells [31].
• Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome [19].
• On the other hand, VEGF increased the production of activin A [27].
• Activin enhanced ACTH-, forskolin-, or dibutyryl-cAMP- but not angiotensin II (Ang II)-induced aldosterone production, whereas BMP-6 specifically augmented Ang II-induced aldosterone production [32].
• The effects of activin A and DHT to increase PSA production were synergistic or additive [28].

Analytical, diagnostic and therapeutic context of INHBE

• This difference in activin inhibition was also evident in an in vitro bioassay because FST288 suppressed, whereas FST315 enhanced, activin-dependent TT cell proliferation [16].
• This activity was eluted at the same retention time as human activin A when fractionated by reversed-phase HPLC [33].
• Mutant follistatins were stably expressed from Chinese hamster ovary cell cultures and assayed for activin binding in a solid-phase competition assay [34].
• Several pieces of evidence, including the immunoblotting analysis and functional assay results, demonstrated the presence of three activin isoforms, A, AB, and B, in the follicular fluid [35].
• The results of this study show that activin A and FS are produced and can be measured by specific enzyme-linked immunosorbent assays in PC3 cells and media but are not detectable in LNCaP cells [36].

References