Señalización y respuestas fisiológicas iniciadas en el antígeno CD53

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Biología Celular, leída el 25-06-2002La presente tesis aporta datos científicos novedosos acerca de las funciones fisiológicas en las que está implicado el antígeno CD53. Tales funciones son activación de las rutas de señalización intracelular correspondientes a las quinasas activadas por mitógenos (MAPK), en diversas líneas celulares, tanto linfoides como epiteliales. Asimismo se describe la expresión del antígeno CD53 en células mesangiales de riñón de rata y el papel que dicho antígeno tiene como inductor de la síntesis de ADN en estas células. Por último, se describe el papel del antígeno CD53 como protector frente a la apoptosis ocasionada por la falta de suero en un linfoma B de rataDepto. de Biología CelularFac. de Ciencias BiológicasTRUEpu

PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.JMR-C received grant support from MINECO-FEDER (SAF2016-78852-R), AESI-ISCIII (PI20CIII/00029) and Spanish Association against Cancer (AECC, CGB14143035THOM). ES group was supported by grants from ISCIII-MCUI (FIS PI19/00934), JCyL (SA264P18-UIC-076), Areces Foundation (CIVP19A5942), Solorzano-Barruso Foundation (FS/32–2020) and by ISCIII-CIBERONC (group CB16/12/00352). Funding to AM group was provided by the Agencia Estatal de Investigación (PID2019-104867RB-I00/AEI/10.13039/501100011033) and by ISCIII-CIBERONC (group CB16/12/00273). TI was supported by grant PID2020-115218RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe” and by ISCIII-CIBERNED. RB received grant support from AESI-ISCIII (PI20CIII/00019). Finally, DP-J and MY groups were supported by grants 1.012.022 (to DP-J), 1.010.929 and 1.400.002 (both to MY) from Fundación Universidad Alfonso X el Sabio (FUAX). All research co-financed by FEDER funds.S

MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury

Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury

Señalización y respuestas fisiológicas iniciadas en el antígeno CD53

La presente tesis aporta datos científicos novedosos acerca de las funciones fisiológicas en las que está implicado el antígeno CD53. Tales funciones son activación de las rutas de señalización intracelular correspondientes a las quinasas activadas por mitógenos (MAPK), en diversas líneas celulares, tanto linfoides como epiteliales. Asimismo se describe la expresión del antígeno CD53 en células mesangiales de riñón de rata y el papel que dicho antígeno tiene como inductor de la síntesis de ADN en estas células. Por último, se describe el papel del antígeno CD53 como protector frente a la apoptosis ocasionada por la falta de suero en un linfoma B de rat

Gene expression of axon growth promoting factors in the deer antler

The annual regeneration cycle of deer (Cervidae, Artiodactyla) antlers represents a unique model of epimorphic regeneration and rapid growth in adult mammals. Regenerating antlers are innervated by trigeminal sensory axons growing through the velvet, the modified form of skin that envelopes the antler, at elongation velocities that reach one centimetre per day in the common deer (Cervus elaphus). Several axon growth promoters like NT-3, NGF or IGF-1 have been described in the antler. To increase the knowledge on the axon growth environment, we have combined different gene-expression techniques to identify and characterize the expression of promoting molecules not previously described in the antler velvet. Cross-species microarray analyses of deer samples on human arrays allowed us to build up a list of 90 extracellular or membrane molecules involved in axon growth that were potentially being expressed in the antler. Fifteen of these genes were analysed using PCR and sequencing techniques to confirm their expression in the velvet and to compare it with the expression in other antler and skin samples. Expression of 8 axon growth promoters was confirmed in the velvet, 5 of them not previously described in the antler. In conclusion, our work shows that antler velvet provides growing axons with a variety of promoters of axon growth, sharing many of them with deer's normal and pedicle skin. © 2010 Pita-Thomas et al.Peer Reviewe

Gene Expression of Axon Growth Promoting Factors in the Deer Antler

The annual regeneration cycle of deer (Cervidae, Artiodactyla) antlers represents a unique model of epimorphic regeneration and rapid growth in adult mammals. Regenerating antlers are innervated by trigeminal sensory axons growing through the velvet, the modified form of skin that envelopes the antler, at elongation velocities that reach one centimetre per day in the common deer (Cervus elaphus). Several axon growth promoters like NT-3, NGF or IGF-1 have been described in the antler. To increase the knowledge on the axon growth environment, we have combined different gene-expression techniques to identify and characterize the expression of promoting molecules not previously described in the antler velvet. Cross-species microarray analyses of deer samples on human arrays allowed us to build up a list of 90 extracellular or membrane molecules involved in axon growth that were potentially being expressed in the antler. Fifteen of these genes were analysed using PCR and sequencing techniques to confirm their expression in the velvet and to compare it with the expression in other antler and skin samples. Expression of 8 axon growth promoters was confirmed in the velvet, 5 of them not previously described in the antler. In conclusion, our work shows that antler velvet provides growing axons with a variety of promoters of axon growth, sharing many of them with deer’s normal and pedicle skin

Deer antler innervation and regeneration

Nervous system injuries are a major cause of impairment in the human society. Up to now, clinical approaches have failed to adequately restore function following nervous system damage. The regenerative cycle of deer antlers may provide basic information on mechanisms underlying nervous system regeneration. The present contribution reviews the actual knowledge on the antler innervation and the factors responsible for its regeneration and fast growth. Growing antlers are profusely innervated by sensory fibers from the trigeminal nerve, which regenerate every year reaching elongation rates up to 2 cm a day. Antler nerves grow through the velvet in close association to blood vessels. This environment is rich in growth promoting molecules capable of inducing and guiding neurite outgrowth of rat sensory neurons in vitro. Conversely, endocrine regulation failed to show effects on neurite outgrowth in vitro, in spite of including hormones of known promoting effects on axon growth. Additional studies are needed to analyze unexplored factors promoting on growth in antlers such as electric potentials or mechanical stretch, as well as on the survival of antler innervating neurons.Peer Reviewe

MicroRNAs detected at the spinal cord of different vertebrates in previous studies [6], [17], [18], [19], [20], [21], [22] but not in the present study.

<p>Note that no data from Liu <i>et al.</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034534#pone.0034534-Liu1" target="_blank">[6]</a> are included in the table because some disagreements were observed among microRNAs with low expression but not among those with high expression (see supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034534#pone-0034534-t001" target="_blank">table 1</a> from Liu <i>et al.</i>).</p

Apoptosis-related microRNAs with significant changes in expression in the present study.

<p>Expression changes, targets and references for the pro-apoptotic and anti-apoptotic microRNAs and those exhibiting dual roles are detailed. For each microRNA, the expression changes in the present study are detailed in column EC (expression changes; D corresponds to downregulation and U to upregulation at the indicated dpo).</p

Negative correlation between microRNA and mRNA expression changes.

<p>Graph illustrating the relationship between the changes in microRNA and mRNA expression 7 days after injury. It clearly shows that mRNA upregulation parallels decreased microRNA expression. Numbers of upregulated and downregulated microRNA data according to the t-tests comparing the injured and sham animals at 7 days after SCI. The mRNA data correspond to the equivalent comparisons (mild plus moderately injured vs. sham at 7 dpo) from DeBiase <i>et al. </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034534#pone.0034534-DeBiase1" target="_blank">[7]</a>.</p