Disease relevance of Inhba

• Follistatin and activin A immunoreactivity were lost in airway epithelial cells in parallel with goblet cell metaplasia [1].
• Non-seminomas contained significantly higher levels of the inhibin betaA subunit (P<0.001) compared with seminomas [2].
• Activin A-induced Tap expression was detected in BMMC but not in RAW264 macrophage-like cells, B16 melanoma cells or P19 embryonic carcinoma cells [3].
• Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified [4].
• The loss of activin/FSH down-regulation leads to prolonged metestrus-diestrus, superovulation, increased numbers of mature follicles, increased offspring, accelerated depletion of primordial follicles, and ultimately premature infertility [5].

High impact information on Inhba

• To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK) [6].
• Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele [6].
• The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin [7].
• Secretion of activin by interstitial cells in the testis [8].
• It is likely that, in the testis, the Leydig cells secrete activin and the Sertoli cells produce inhibin, or a combination of both [8].

Biological context of Inhba

• Thus, the enlarged islets and beta cell number likely result from increased activin action [9].
• Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line [10].
• Although both activin and glucocorticoids are notable regulators of FSHbeta by themselves, we find that cotreatment results in a synergistic interaction on the mouse FSHbeta promoter at the level of the gonadotrope using transient transfection of a reporter gene into the LbetaT2 immortalized gonadotrope-derived cell line [10].
• In vitro, the biological effects of activin A are neutralized by the soluble binding protein follistatin [1].
• The kinetics and distribution of activin A and follistatin protein were assessed in lung tissue and bronchoalveolar lavage fluid and measured in relation to airway eosinophilia, goblet cell metaplasia and Th2 cytokine production in mediastinal lymph nodes [1].

Anatomical context of Inhba

• Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells [11].
• These cell lines include mesodermal (MES-1), neuroepithelial (EPI-7), and visceral endoderm-like (END-2) cell types, expressing both inhibin beta A and beta B subunit mRNAs [12].
• By contrast, two species (6 and 3 kb) of activin receptor ActRII mRNA were identified in equal intensity in all four Leydig tumor cell lines [13].
• Identification of tocopherol-associated protein as an activin/TGF-beta-inducible gene in mast cells [3].
• Activin may also play a positive role in oocyte maturation and acquisition of developmental competence [14].

Associations of Inhba with chemical compounds

• Concomitantly, activin, TGF-beta and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles [14].
• TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors [15].
• Hippocampal neurons from dnActRIB mice were significantly more vulnerable to intracerebroventricular injection of the excitotoxin kainic acid than those from control littermates, indicating a crucial role of endogenous activin in the rescue of neurons from excitotoxic insult [16].
• Xlmx1b was found to be upregulated by activin A and RA inhibited this upregulation in a concentration dependant manner [17].
• Second, SB203580 inhibited the inhibitory effect of activin A on the colony-forming activity of K562 cells using the methylcellulose colony assay, indicating that activin A inhibits K562 colony formation by activating p38 MAPK [18].

Physical interactions of Inhba

• The effects of recombinant human activin A and its binding protein follistatin on odontoblast differentiation were also studied in cultures of dental papillae (DP) isolated from the mandibular first molars of E-17-day mice [19].
• In early Xenopus embryos, the prototypical XFast-1/Smad2/Smad4 complex ARF1 is induced at the Mix.2 ARE by activin overexpression [20].

Regulatory relationships of Inhba

• Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles [21].
• Smad2 is a receptor-regulated Smad that is activated specifically by transforming growth factor beta and activin signaling [22].
• Exogenous activin A stimulated the mRNA expression and gelatinolytic activity of matrix metalloproteinase-2 (MMP-2) in macrophages in both the presence and the absence of LPS [23].
• To test this possibility, we generated transgenic mice that overexpress the activin betaA chain in the epidermis under the control of a keratin 14 promoter [24].
• The promotion of plasmacytoma tumor growth by mesenchymal stroma is antagonized by basic fibroblast growth factor induced activin A [25].
• Activin A stimulation of ER expression was a direct effect at the level of gene transcription, as it was not abolished by cycloheximide but was abolished by actinomycin D, and in transfected granulosa cells activin A stimulated ERalpha promoter activity [26].

Other interactions of Inhba

• Developmental expression of activin/inhibin beta A, beta B, and alpha subunits, and activin receptor-IIB genes in preimplantation mouse embryos [27].
• This soluble form of BMP receptor (sBMPR) was in monomer form in solution and bound to BMP-4 but not to activin or transforming growth factor-beta1 [28].
• The effect of external signals on myogenic differentiation of BLC6 cells was demonstrated by cocultivation with visceral endodermal END-2 cells and the activin A-secreting WEHI-3 cells [29].
• Inhibins differentially antagonize activin and bone morphogenetic protein action in a mouse adrenocortical cell line [30].
• In the ascidian, Halocynthia roretzi, treatment with bFGF of presumptive-notochord blastomeres that had been isolated at the early 32-cell stage promoted the formation of notochord at a low concentration of bFGF (0.02 ng/ml), while activin failed to induce notochord differentiation [31].

Analytical, diagnostic and therapeutic context of Inhba

• Northern blot analysis revealed inhibin beta A and beta B mRNA expression in these cells [32].
• Tocopherol-associated protein (Tap) was one of the induced genes, and the Tap induction in response to activin A treatment was confirmed by real-time RT-PCR analyses [3].
• The cDNA microarray analyses indicated that in BMMC, five genes were induced by treatment with 4 nM activin A for 2 h [3].
• Southern blot analysis indicates that only one gene for EDF/inhibin beta A exists in the human genome [33].
• In Western blot analysis, immunoreactive activin A was detected in the culture medium only when the macrophages were stimulated by LPS [23].

References