Hormona anti-Mülleriana en felinos domésticos / Anti-Müllerian hormone in domestic felids

La hormona anti-Mülleriana (HAM) es una glicoproteína dimérica de 140 kDa que pertenece a la superfamilia del factor de crecimiento transformante ß. La HAM es producida por las células de Sertoli de los testículos fetales siendo responsable de la regresión de los conductos müllerianos durante la diferenciación sexual masculina. En la hembra la HAM circula a niveles casi indetectable al nacer, con un ligero aumento en los primeros años de vida hasta la pubertad cuando se expresa en las células de la granulosa de folículos preantrales y antrales pequeños del ovario. En hembras adultas, la HAM actúa como un regulador autocrino y paracrino inhibiendo el reclutamiento de folículos primordiales y reduciendo la respuesta a la hormona folículo estimulante. En el gato doméstico el número de estudios de HAM es muy escaso quedando aún abundantes aspectos por definir en la especie. También la validación de un único inmunoensayo que permita la comparación de valores séricos entre los trabajos es necesaria. El objetivo de esta revisión fue explicar aspectos básicos de la fisiología de la HAM y resumir las principales publicaciones en el gato doméstico. Finalmente, se proponen aplicaciones prácticas para esta hormona en la especie.(AU)

O hormônio anti-Mülleriano (HAM) é uma glicoproteína dimérica de 140 kDa que pertence a superfamília do fator de crescimento transformador ß. O HAM é produzido pelas células de Sertoli dos testículos fetais, sendo responsável pela regressão dos ductos de Müller durante a diferenciação sexual masculina. Na fêmea, o HAM circula a níveis quase indetectáveis ao nascimento, com um ligeiro aumento nos primeiros anos de vida até a puberdade, quando se expressa nas células da granulosa de folículos préantrais e antrais pequenos do ovário. Nas fêmeas adultas, o HAM atua como um regulador autócrino e parácrino inibindo o recrutamento de folículos primordiais e reduzindo a resposta ao hormônio folículoestimulante. No gato doméstico o número de estudos do HAM é muito escasso, faltando vários aspectos a serem definidos na espécie. Também é necessária a validação de um único imunoensaio que permita a comparação de valores séricos entre trabalhos. O objetivo desta revisão foi explicar aspectos básicos da fisiologia do HAM e resumir as principais publicações no gato doméstico. Finalmente, se propõe aplicações práticas para este hormônio na espécie.(AU)

Controlling burst effect with PLA/PVA coaxial electrospun scaffolds loaded with BMP-2 for bone guided regeneration.

Biocompatible scaffolds have been used to promote cellular growth and proliferation in order to develop grafts, prostheses, artificial skins and cartilage. Electrospinning is widely studied as a method capable of producing nanofibers which enables cell attachment and proliferation, generating a functional scaffold that is suitable for many types of organs or tissues. In this study, electrospinning was used to obtain core-shell and monolithic fibers from the biocompatible poly (lactic acid) and poly (vinyl alcohol) polymers. The main purpose of this work is to produce core-shell nanofiber based scaffolds that works as a sustained delivery vehicle for BMP-2 protein, allowing those fibers to be used in the recovery of alveolar bone tissue without further bone surgery. Then, polymer nanofibers were manufactured by optimizing process parameters of coaxial electrospinning with emphasis on the most relevant ones: voltage, internal and external flows in an attempt to correlate fibers properties with protein releasing abilities. All nanofibers were characterized according to its morphology, thermal behaviour, crystallinity and release profile. For the release tests, bovine albumin was added into internal fiber for future periodontal restorage application. Obtained results demonstrate that fibers were formed with diameters up to 250 nm. According to electronic microscopy images, one could observe surface of nanofibers, thickness and core-shell morphology confirmed. X-ray diffraction analysis and contact angle tests showed fibers with low crystal degree and low hydrophobicity. Nanofibers structure affected in vitro release model tests and consequently the cellular assays.

Transforming Growth Factor-Beta Family: Advances in Vascular Function and Signaling.

This review includes a comprehensive, but succinct, summary on the essentials of TGF- ß structure, family members, receptors, and intracellular mediators. Also provided is a select list of original publications that report novel roles and facets of TGF-ß in vascular function and signaling in the contexts of health and disease.

TGF- ß: an important mediator of allergic disease and a molecule with dual activity in cancer development.

The transforming growth factor- ß (TGF- ß ) superfamily is a family of structurally related proteins that includes TGF- ß , activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF- ß superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF- ß is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF- ß receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF- ß with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as "allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF- ß is involved. Here, we review recent studies that suggest an important role for TGF- ß in both allergic disease and cancer progression.

Betaglycan has two independent domains required for high affinity TGF-beta binding: proteolytic cleavage separates the domains and inactivates the neutralizing activity of the soluble receptor.

Betaglycan is a coreceptor for members of the transforming growth factor beta (TGF-beta) superfamily. Mutagenesis has identified two ligand binding regions, one at the membrane-distal and the other at the membrane-proximal half of the betaglycan ectodomain. Here we show that partial plasmin digestion of soluble betaglycan produces two proteolysis-resistant fragments of 45 and 55 kDa, consistent with the predicted secondary structure, which indicates an intervening nonstructured linker region separating the highly structured N- and C-terminal domains. Amino terminal sequencing indicates that the 45 and 55 kDa fragments correspond, respectively, to the membrane-distal and -proximal regions. Plasmin treatment of membrane betaglycan results in the production of equivalent proteolysis-resistant fragments. The 45 and 55 kDa fragments, as well as their recombinant soluble counterparts, Sol Delta10 and Sol Delta11, bind TGF-beta, but nonetheless, compared to intact soluble betaglycan, have a severely diminished ability to block TGF-beta activity. Surface plasmon resonance (SPR) analysis indicates that soluble betaglycan has K(d)'s in the low nanomolar range for the three TGF-beta isoforms, while those for Sol Delta10 and Sol Delta11 are 1-2 orders of magnitude higher. SPR analysis further shows that the K(d)'s of Sol Delta11 are not changed in the presence of Sol Delta10, indicating that the high affinity of soluble betaglycan is a consequence of tethering the domains together. Overall, these results suggest that betaglycan ectodomain exhibits a bilobular structure in which each lobule folds independently and binds TGF-beta through distinct nonoverlapping interfaces and that linker modification may be an approach to improve soluble betaglycan's TGF-beta neutralizing activity.

Anticipation in familial lattice corneal dystrophy type I with R124C mutation in the TGFBI (BIGH3) gene.

PURPOSE: To report the clinical, ophthalmic, and genetic characteristics for lattice corneal dystrophy type I (LCDI) in a Chilean family. METHODS: Six affected family members were examined clinically including visual acuity, color cornea photography, applanation tonography, and fundoscopy. Genomic DNA was extracted from peripheral leukocytes from six affected and three unaffected members of a family with lattice corneal dystrophy type I. Exon 4 of the transforming growth factor-induced gene (TGFBI) was screened for the most frequent mutation, R124C, in the proband by sequencing. We also designed a rapid polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze the same mutation, amplifying exon 4 and digesting with PstI restriction enzyme. Using this strategy, we analyzed the mutation in six affected and three healthy family members. RESULTS: Three generations of family members were positively diagnosed with lattice corneal dystrophy. Six participants demonstrated LCD1 in both eyes, most of whom were symmetric. Age at onset of symptoms was variable (3-42 years old). Moreover, in this family, the age of onset of the disease decreased in succeeding generations, which could be interpreted as anticipation. Visual acuity varied from 1.0 to 0.13. Two patients, ages 69 and 44 years old, demonstrated a degree of severity "Bad" according to best-corrected vision and corneal commitment. The exon 4 sequence of TGFBI of the proband exhibits the heterozygous single-nucleotide mutation, C417T, leading to amino acid substitution (R124C) in the encoded TGF-induced protein. Using PCR-RFLP, we confirmed the heterozygous mutation in six affected family members and excluded it in three healthy members. CONCLUSIONS: The R124C mutation in TGFBI cosegregated with LCD type I in the investigated family. This is the first report of a molecular analysis of LCD type I in Chilean patients. The early onset affected persons in the fourth generation raises the possibility of anticipation.

E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence.

Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer.