Eduardo Martínez-Martínez | National Institute of Genomic Medicine, Mexico (original) (raw)

Papers by Eduardo Martínez-Martínez

PeerJ

Background High fructose exposure induces metabolic and endocrine responses in adipose tissue. Re... more Background High fructose exposure induces metabolic and endocrine responses in adipose tissue. Recent evidence suggests that microRNAs in extracellular vesicles are endocrine signals secreted by adipocytes. Fructose exposure on the secretion of microRNA by tissues and cells is poorly studied. Thus, the aim of this study was to evaluate the effect of fructose exposure on the secretion of selected microRNAs in extracellular vesicles from 3T3-L1 cells and plasma from Wistar rats. Methods 3T3-L1 cells were exposed to 550 µM of fructose or standard media for four days, microRNAs levels were determined in extracellular vesicles of supernatants and cells by RT-qPCR. Wistar rats were exposed to either 20% fructose drink or tap water for eight weeks, microRNAs levels were determined in extracellular vesicles of plasma and adipose tissue by RT-qPCR. Results This study showed that fructose exposure increased the total number of extracellular vesicles released by 3T3-L1 cells (p = 0.0001). The ...

International Journal of Molecular Medicine

Journal of Extracellular Vesicles

Frontiers in Neurology

Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative... more Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Moreover, EVs have the capacity to modify the physiology of neuronal circuits by transferring proteins, RNA, lipids, and metabolites. The proteomic characterization of EVs (exosomes and microvesicles) from preclinical models and patient samples has the potential to reveal new proteins and molecular networks that affect the normal physiology prior to the appearance of traditional biomarkers of neurodegeneration. Noteworthy, many of the genetic risks associated to the development of Alzheimer's and Parkinson's disease affect the crosstalk between mitochondria, endosomes, and lysosomes. Recent research has focused on determining the role of endolysosomal trafficking in the onset of neurodegenerative diseases. Proteomic studies indicate an alteration of biogenesis and molecular content of EVs as a result of endolysosom...

Frontiers in Neuroscience

Castillo et al. Neurodegeneration Revisited cognitive impairment, dementia, and cerebrovascular e... more Castillo et al. Neurodegeneration Revisited cognitive impairment, dementia, and cerebrovascular events such as stroke. Second, we suggest that the persistence of senescent cells in neuronal circuits may favor, together with systemic metabolic diseases, neurodegeneration to occur. Third, we argue that neurodegeneration may start in response to altered body and brain trophic interactions established via the hardwire that connects peripheral targets with central neuronal structures or by means of extracellular vesicle (EV)-mediated communication. Lastly, we elaborate on how lifespan body dysbiosis may be linked to the origin of neurodegeneration. We highlight the existence of bacterial products that modulate the gut-brain axis causing neuroinflammation and neuronal dysfunction. As a concluding section, we end by recommending research avenues to investigate these etiological paths in the future. We think that this requires an integrated, interdisciplinary conceptual research approach based on the investigation of the multimodal aspects of physiology and pathophysiology. It involves utilizing proper conceptual models, experimental animal units, and identifying currently unused opportunities derived from human data. Overall, the proposed etiological paths and experimental recommendations will be important guidelines for future cross-discipline research to overcome the translational roadblock and to develop causative treatments for neurodegenerative diseases.

The American journal of pathology, Jan 18, 2017

Calcium content in patients with calcific aortic valve disease (CAVD) correlates with the severit... more Calcium content in patients with calcific aortic valve disease (CAVD) correlates with the severity of stenosis. In CAVD, activated T lymphocytes localize with osteoclast regions; however, the functional consequences of this association remain unknown. We hypothesized that CD8(+) T cells modulate calcification in CAVD. Explanted CAVD valves (n = 52) dissected into noncalcified and calcified portions were subjected to mRNA extraction, real-time quantitative PCR, enzyme-linked immunosorbent assay, and immunohistochemical analyses. Compared with noncalcified portions, calcified regions exhibited significantly elevated transcripts for CD8, interferon (IFN)-γ, CXCL9, Perforin 1, Granzyme B, and heat shock protein 60. Osteoclast-associated receptor activator of NK-κB ligand (RANKL), tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated receptor increased significantly, whereas Cathepsin K remained unchanged. The stimulation of tissue segments with phorbol-12-myristate-13-ac...

BioMed Research International, 2016

Circulating microRNAs (miRNAs) and the functional implications of miRNAs contained in extracellul... more Circulating microRNAs (miRNAs) and the functional implications of miRNAs contained in extracellular vesicles (EVs) have gained attention in the last decade. Little is known about the regulation of the abundance of plasma miRNAs in response to chronic ingestion of carbohydrates. Therefore, we explored the circulating levels of miR-21, miR-146a, miR-155, and miR-223 in rats consuming sucrose in drinking water. Weanling Wistar rats were 25 weeks with 30% sucrose in drinking water, and miRNAs expression was determined in total plasma and in microvesicles, by RT-qPCR with TaqMan probe based assays for miR-21, miR-146a, miR-155, and miR-223, using cel-miR-39 (as spike in control and reference). Endotoxemia was also measured. Sucrose-fed animals showed higher body weight and retroperitoneal adipose tissue as well as higher glucose and triglyceride plasma levels than controls. Plasma endotoxin levels were low and not different among groups. Plasma miR-21 and miR-223 were higher in the sucro...

The Journal of Physiology, 2016

is an Editorial Board Member of several scientific journals and has authored over 150 manuscripts... more is an Editorial Board Member of several scientific journals and has authored over 150 manuscripts on cardiovascular pathobiology. Her current research focuses on the mechanisms of vascular calcification and calcific aortic valve disease. This review was presented at the symposium "Extracellular vesicles, exosomes and microparticles in cardiovascular disease", which took place at

Phenotype plasticity is by far the most important property of living beings. In no other organ sy... more Phenotype plasticity is by far the most important property of living beings. In no other organ system plasticity has been the focus of such an intense scrutiny than in the nervous system. This is not surprising since constant neural reorganization is assumed to support, for instance, adaptive behavioral responses, individual differences of behavior and numerous neurological disease states (e.g., the phantom limb). With such a long history of research, the study of neural plasticity has already generated explanatory claims that many conceived as general principles that rule neural plastic responses. Information arising from developmental sensory neurobiology is, however, Correspondence/Reprint request: Dr.

Molecular Biology of Valvular Heart Disease, 2014

Discoidin domain receptors (DDRs)-1 and 2 are a family of 2 receptor tyrosine kinases that exhibi... more Discoidin domain receptors (DDRs)-1 and 2 are a family of 2 receptor tyrosine kinases that exhibit substrate specificity for both fibrillar and nonfibrillar collagens. 9 DDR activity has been implicated in physiological processes such as cell migration, 10 differentiation, 11 and ECM remodeling, 12 whereas dysregulated DDR function has been linked to the progression of fibrosis, arthritis, and cancer. 13 DDR-1, composed of 5 membrane-bound and 2 secreted isoforms generated by alternative splicing, 14 was found to play a complex role in the Objective-Collagen accumulation and calcification are major determinants of atherosclerotic plaque stability. Extracellular vesicle (EV)-derived microcalcifications in the collagen-poor fibrous cap may promote plaque rupture. In this study, we hypothesize that the collagen receptor discoidin domain receptor-1 (DDR-1) regulates collagen deposition and release of calcifying EVs by vascular smooth muscle cells (SMCs) through the transforming growth factor-β (TGF-β) pathway. Approach and Results-SMCs from the carotid arteries of DDR-1 −/− mice and wild-type littermates (n=5-10 per group) were cultured in normal or calcifying media. At days 14 and 21, SMCs were harvested and EVs isolated for analysis. Compared with wild-type, DDR-1 −/− SMCs exhibited a 4-fold increase in EV release (P<0.001) with concomitantly elevated alkaline phosphatase activity (P<0.0001) as a hallmark of EV calcifying potential. The DDR-1 −/− phenotype was characterized by increased mineralization (Alizarin Red S and Osteosense, P<0.001 and P=0.002, respectively) and amorphous collagen deposition (P<0.001). We further identified a novel link between DDR-1 and the TGF-β pathway previously implicated in both fibrotic and calcific responses. An increase in TGF-β1 release by DDR-1 −/− SMCs in calcifying media (P<0.001) stimulated p38 phosphorylation (P=0.02) and suppressed activation of Smad3. Inhibition of either TGF-β receptor-I or phospho-p38 reversed the fibrocalcific DDR-1 −/− phenotype, corroborating a causal relationship between DDR-1 and TGF-β in EV-mediated vascular calcification. Conclusions-DDR-1 interacts with the TGF-β pathway to restrict calcifying EV-mediated mineralization and fibrosis by SMCs. We therefore establish a novel mechanism of cell-matrix homeostasis in atherosclerotic plaque formation. (Arterioscler Thromb Vasc Biol. 2016;36:525-533. (M.P.B.). The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl/

We describe a stereology method to obtain reliable estimates of the total number of proliferative... more We describe a stereology method to obtain reliable estimates of the total number of proliferative and migratory epithelial cells after wounding. Using pulse and chase experiments with halogenated thymidine analogs such as iododeoxyuridine (IdU) and chlorodeoxyuridine (CldU), it is possible to track epithelial populations with heterogeneous proliferative characteristics through skin compartments. The stereological and tissue processing methods described here apply widely to address important questions of skin stem-cell biology.

Neuroscience, Jan 1, 2005

Abstract—Metabolic indices of neuronal activity are thought to predict changes in the frequency o... more Abstract—Metabolic indices of neuronal activity are thought
to predict changes in the frequency of action potentials.
There are stimuli that do not shift action potential frequency
but change the temporal organization of neuronal firing following
modifications of excitatory inputs by inhibitory synaptic
activation. To our knowledge it is unknown whether this
kind of stimulus associates with adjustments of metabolic
markers of neuronal activity. Here, we used the hypothalamic–
neurohypophysial system of lactating rats to address whether
shifts in the temporal organization of neuronal firing relate
with modifications of metabolic markers of neuronal activity.
Cytochrome oxidase activity, 3H-2-deoxyglucose uptake, and
the area occupied by blood vessels increased in the paraventricular nucleus and neurohypophysis of lactating rats, as
compared with their virgin counterparts. Taken together,
these results suggest that metabolic demands denote shifts
in the temporal organization of action potentials related with
the adjustment of excitatory synaptic activation, and support
that changes in metabolic markers do not necessarily reflect
shifts in the frequency of action potentials. © 2005 Published
by Elsevier Ltd on behalf of IBRO.

The cellular strategy leading to formation of neuronal circuits in the rodent barrel cortex is st... more The cellular strategy leading to formation of neuronal circuits in the rodent barrel cortex is still a matter of controversy. Both selective and constructive mechanisms have been proposed. The selective mechanism involves an overproduction of neuronal processes and synapses followed by activity dependent pruning. Conversely, a constructive mechanism would increase the number of axons, dendrites, and synapses during development to match functionality. In order to discern the contributions of these two mechanisms in establishing a neuronal circuit in the somatosensory cortex, morphometric analysis of dendritic and axonal arbor growth was performed. Also, the number of synapses was followed by electron microscopy during the first month of life. We observed that axonal and dendritic arbors retracted distal branches, and elongated proximal branches, resulting in increased arbor complexity. This neuronal remodeling was accompanied by the steady increase in the number of synapses within barrel hollows. Similarly, the content of molecular markers for dendrites, axons and synapses also increased during this period. Finally, cytochrome oxidase activity rose with age in barrels indicating that the arbors became more complex while synapse density and metabolic demands increased. Our results support the simultaneous use of both selective and constructive mechanisms in establishing the barrel cortex circuitry. in SciRes. http://www.scirp.org/journal/abb

PloS one, 2013

Birth-enucleated rodents display enlarged representations of whiskers (i.e., barrels of the poste... more Birth-enucleated rodents display enlarged representations of whiskers (i.e., barrels of the posteromedial subfield) in the primary somatosensory cortex. Although the historical view maintains that barrel expansion is due to incremental increases in neuronal activity along the trigeminal pathway during postnatal development, recent evidence obtained in experimental models of intramodal plasticity challenges this view. Here, we re-evaluate the role of experience-dependent neuronal activity on barrel expansion in birth-enucleated rats by combining various anatomical methods and sensory deprivation paradigms. We show that barrels in birth-enucleated rats were already enlarged by the end of the first week of life and had levels of metabolic activity comparable to those in control rats at different ages. Dewhiskering after the postnatal period of barrel formation did not prevent barrel expansion in adult, birth-enucleated rats. Further, dark rearing and enucleation after barrel formation did not lead to expanded barrels in adult brains. Because incremental increases of somatosensory experience did not promote barrel expansion in birth-enucleated rats, we explored whether shifts of the developmental timing could better explain barrel expansion during the first week of life. Accordingly, birth-enucleated rats show earlier formation of barrels, accelerated growth of somatosensory thalamocortical afferents, and an earlier H4 deacetylation. Interestingly, when H4 deacetylation was prevented with a histone deacetylases inhibitor (valproic acid), barrel specification timing returned to normal and barrel expansion did not occur. Thus, we provide evidence supporting that shifts in developmental timing modulated through epigenetic mechanisms, and not increased levels of experience dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

PloS one, 2012

Background: The legal framework and funding mechanisms of the national health research system wer... more Background: The legal framework and funding mechanisms of the national health research system were recently reformed in Mexico. A study of the resource allocation for health research is still missing. We identified the health research areas funded by the National Council on Science and Technology (CONACYT) and examined whether research funding has been aligned to national health problems.

PLOS One, 2012

Background: The bulge region of the hair follicle contains resident epithelial stem cells (SCs) t... more Background: The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing.

Proceedings of the …, Jan 1, 2008