Browsing by Subject "Repair"

Now showing 1 - 4 of 4
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    Evolutionary trade-offs in kidney injury and repair
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Lei, Yutian; Anders, Hans Joachim
    Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environmentphenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.
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    MRL/MpJ mice show unique pathological features after experimental kidney injury
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Shiozuru, Daichi; Ichii, Osamu; Kimura, Junpei; Nakamura, Teppei; Ali Elewa, Yaser Hosny; Otsuka-Kanazawa, Saori; Kon, Yasuhiro
    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1- positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury
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    Olig2 knockdown alleviates hypoxic- ischemic brain damage in newborn rats
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Yang, Lijun; Cui, Hong
    Objectives. Neuronal damage is an important pathological mechanism in neonatal hypoxic-ischemic brain damage (HIBD). We found in our previous studies that oligodendrocyte transcription factor 2 (Olig2) downregulation was able to increase cell survival in the brain. However, the specific mechanism has yet to be clarified. Methods. Sprague-Dawley rats aged 3 d were randomly divided into three groups: the normal control group, the Olig2-RNAi group, and the RNAi-negative control group. The normal control group received no treatment, the Olig2-RNAi group received the Olig2 RNAi adenovirus, and the RNAi-negative control group was given the control adenovirus after the completion of the HIBD model. Infarct lesions and their volumes were observed by triphenyltetrazolium chloride (TTC) staining 3 d after the completion of the adenovirus local injection. The condition of the tissue was characterized by hematoxylin-eosin staining 7 d after the model was established, and cell viability was determined by azure methylene blue staining. Subcellular damage was analyzed by transmission electron microscopy. Rotarod analysis was performed to detect moving behavior ability and an Morris water maze assay was conducted to evaluate the memory. Results. TTC staining showed a smaller brain injury area in the Olig2-RNAi group than in the RNAi-negative control group. Hematoxylin-eosin staining indicated the presence of severe cell injury in the hippocampal region after HIBD, which improved after Olig2 knockdown. Azure methylene blue staining and electron microscopy results suggested that the cells improved after Olig2 knockdown. The rats stayed longer on the rotating rod, and their latency in the water maze test was gradually shortened relative to that of the rats in the Olig2-RNAi negative control group. Conclusion. Olig2 knockdown can promote the repair of hypoxic-ischemic brain damage in newborn rats.
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    Villous trophoblast of human placenta: a coherent view of its turnover, repair and contributions to villous development and maturation
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Mayhew, T. M.
    J\ coh e re nt vicw o f hum a n v illou s trophoblast as a continuously renewing epithelium is presented. Epithelia undergoing continuous rcnewal (e.g. intestinal mucosa, epidermis) display clonogenic ce lls which pass throug h sevc ral transit di visions be fore migrating out of proliferation zones and into zones of maturati on/differenti ati on. Quantitative relations (e.g. re lati ve numbers of cells) betwee n proliferati on and diffe rentiation zones help to define the steady state and this may va ry in res po nse to ph ysi o log ic al and pathological circumstances. From the differenti ati on compartment, ce lls or ce ll fr agments arc eve ntu all y extruded by mechanisms which may involve apoptosis. All these features are seen in trophoblastic epithelium. Cy totrophobl ast ce lls (CT, proliferation zone) divide continuously throughout gestation and post-mitotic cells are recruitcd into syncytiotrophoblast (ST, diffe rentiation zone) aft cr membrane fusion. Evidence of fu sion events includes localised confluence of CT and ST cytoplasms, and intrasy ncyti al plasma membrane segments bearing desmosomal remn ants. During diffe renti ati on, nu clei undergo changes in shape, chromatin condensation and packing densit y. Densely-clustered nuclei are associated with cy tokeratin intermed iate fil aments and annul ate lamellae . Both clustered and non-clustered nuclei show ultrastructural fea tures of pre-apoptosis and apoptosis. Normall y, apoptosis is triggered only when nuclei are in the syncytium. Some (pre-)apoptotic nuclear aggregates are se qu este red in sy nc yti a l knots, extrud ed as troph obl ast fr agments into the intervill ous space and th e n depo rt ed int o th e mate rn a l c irc ul ati o n to be ph agocytosed at extrapl acental sites. During gestation, there is some constancy in the numerical ratios between CT and ST nuclei pointing to a normal steady state. The steady state may be perturbed when the epithelium is damaged loca ll y. Whe re the epithelium is denud ed, fibrin-type fibrinoid from the intervillous space plugs the discontinuity and , with CT proliferation, facilitates reepitheli alisation. Features of normal villous development (e.g. sprouting, int ervillous bridge formati on, bridge abrupt ion, sy ncytial knot formation) arc explicable in the co nt ex t of tr o ph obl ast turn ove r with ea rl y CT pro li fe rati o n be in g ma inl y fo r g row th a nd la te r proliferation for renewa l and repair. Adaptive re-settings of the epithelial steady state may also occur in abnormal pregnancies.