Extracellular Matrix Dynamics in Hepatocarcinogenesis: a Comparative Proteomics Study of PDGFC Transgenic and Pten Null Mouse Models

We are reporting qualitative and quantitative changes of the extracellular matrix (ECM) and associated receptor proteomes, occurring during the transition from liver fibrosis and steatohepatitis to hepatocellular carcinoma (HCC). We compared two mouse models relevant to human HCC: PDGFC transgenic (Tg) and Pten null mice, models of disease progression from fibrosis and steatohepatitis to HCC. Using mass spectrometry, we identified in the liver of both models proteins for 26 collagen-encoding genes, providing the first evidence of expression at the protein level for 16 collagens. We also identified post-transcriptional protein variants for six collagens and lysine hydroxylation modifications for 14 collagens. Tumor-associated collagen proteomes were similar in both models with increased expression of collagens type IV, VI, VII, X, XIV, XV, XVI, and XVIII. Splice variants for Col4a2, Col6a2, Col6a3 were co-upregulated while only the short form of Col18a1 increased in the tumors. We also identified tumor specific increases of nidogen 1, decorin, perlecan, and of six laminin subunits. The changes in these non-collagenous ECM proteins were similar in both models with the exception of laminin β3, detected specifically in the Pten null tumors. Pdgfa and Pdgfc mRNA expression was increased in the Pten null liver, a possible mechanism for the similarity in ECM composition observed in the tumors of both models. In contrast and besides the strong up-regulation of integrin α5 protein observed in the liver tumors of both models, the expression of the six other integrins identified was specific to each model, with integrins α2b, α3, α6, and β1 up-regulated in Pten null tumors and integrins α8 and β5 up-regulated in the PDGFC Tg tumors. In conclusion, HCC–associated ECM proteins and ECM–integrin networks, common or specific to HCC subtypes, were identified, providing a unique foundation to using ECM composition for HCC classification, diagnosis, prevention, or treatment

Pseudomonas putida en la biotecnología industrial: Avances recientes y orientaciones futuras

Gram-negative, rod-shaped Pseudomonas putida bacteria may be found in a variety of biological environments. This ubiquity can be attributed to its extraordinarily adaptable metabolism, ability to endure physicochemical stress, and propensity to survive in unfavorable conditions. These traits have led to an increase in interest in microorganisms for industrial usage, also associated with studying has advanced quickly in recent years. Strong motivators in this regard include use of inexpensive waste streams and sustainable feedstocks for manufacturing with added value compounds along with continual advancement of Systematic biology of this bacterium and genetic strain engineering. Here, provide a summary of current developments and future directions P. putida is used as a cell factory in genetic engineering, computer systems, and synthetic biology.La bacteria Pseudomonas putida, gramnegativa y con forma de bastoncillo, puede encontrarse en una gran variedad de entornos biológicos. Esta ubicuidad puede atribuirse a su metabolismo extraordinariamente adaptable, su capacidad para soportar estrés fisicoquímico y su propensión a sobrevivir en condiciones desfavorables. Estos rasgos han provocado un aumento del interés por los microorganismos de uso industrial, cuyo estudio también ha avanzado rápidamente en los últimos años. Entre las principales motivaciones a este respecto se encuentran el uso de flujos de residuos baratos y materias primas sostenibles para la fabricación de compuestos con valor añadido, junto con el avance continuo de la biología sistemática de esta bacteria y la ingeniería genética de cepas. Aquí se ofrece un resumen de los avances actuales y las direcciones futuras P. putida se utiliza como fábrica celular en ingeniería genética, sistemas informáticos y biología sintética