Browsing by Subject "Tissue remodeling"

Now showing 1 - 3 of 3
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    Molecular changes underlying pulmonary emphysema and chronic bronchitis in Chronic Obstructive Pulmonary Disease: An updated review
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Baltazar García, Elia A.; Vargas Guerrero, Belinda; Gasca Lozano, Luz E.; Gurrola Díaz, Carmen M.
    The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-β/Smad or Wnt/β-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.
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    Prevention of colon enlargement by TNF-α antagonist in a streptozotocin-induced diabetic rat model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Sholikah, Tri Agusti; Septyaningtrias, Dian Eurike; Sumiwi, Yustina Andwi Ari; Muthmainah, M.; Susilowati, Rina
    Summary. Purpose. We investigated the effect of tumor necrosis factor (TNF)-α antagonist on the structure and function of the streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat colon. Methods. Thirty rats were divided into normal control (NC), diabetic control (DC), and diabetic etanercept (DE) groups. The DE group was injected with etanercept twice a week. Blood glucose, body weight, fecal pellet, colonic transit time, and plasma TNF-α were measured. The colon was dissected out, followed by weight and length measurements. Toluidine blue and Verhoeff’s staining, immunohistochemistry for TNF-α, RAGE, iNOS, arginase, and western blot for RAGE were performed on the colonic tissue. Results. Administration of TNF-α antagonist had no significant effect on the body weight and blood glucose level of the diabetic groups. However, the DE group had a shorter and lighter colon and less coarse and less dense collagen fibers in the submucosal layer than the DC group. Weaker immunoreactivity of TNF-α, RAGE, iNOS, and arginase I was observed in colon tissue sections of the DE groups compared with the DC group. Although the etanercept effect on colonic function was not significantly different, the preventive effect size of etanercept on colon remodeling was considerably large, as shown by calculated-Cohen’s d>0.8. Conclusions. TNF-α signaling in the colonic tissue of diabetic rats has a strong effect on tissue remodeling, leading to colon enlargement. TNF-α antagonists may be beneficial in preventing diabetic-related pathology in the colon in combination with anti-diabetic drugs
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    Transcription regulators are transiently expressed during the prostate gland adaptation to the hypoandrogenic environment
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Nishan, Umar; Rosa Ribeiro, Rafaela; Lenz Cesar, Carlos; Carvalho, Hernandes F.
    The high incidence of prostatic diseases, including malignant tumors, makes the understanding of prostate biology very important. Androgen deprivation, blockade by orchiectomy, or chemical castration causes prostate and tumor shrinkage. The gene networks involved in a cell type-specific fashion are rather unknown. This work was undertaken to identify genes with annotated function in transcription regulation that might define transitions in gene expression. A total of 15 potential regulatory genes were identified. Validation by qRT-PCR showed that Zfp703 and Arid1a exhibit expression maxima at day 1; Ash2l, Nelf, Pbx3, Eya2 at day 4; Dmrt2 at day 5 and Lbh and Sox1 at day 7 after castration. Using immunohistochemistry, we further determined that PBX3 was found in both stromal and epithelial cells, whereas ARID1A and NELF were restricted to the epithelium, and DMRT2 and EYA2 were exclusively found in the stroma. Though the proteins ZFP703 and ASH2l were not found in any experimental condition, their mRNAs were located by in situ hybridization in both epithelium and stroma. In conclusion, androgen deprivation triggers the expression of temporally regulated gene sets in both epithelial and stromal cells. These gene subsets will help establish the regulatory gene expression programs orchestrating the castration-induced remodeling of the prostate gland, and represent putative targets to increase the efficacy of androgen-deprivation to induce epithelial (and cancer) cell death.