Histology and histopathology Vol.31, nº2 (2016)
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- PublicationOpen AccessCo-localization of the zinc transporter ZnT8 (slc30A8) with ghrelin and motilin in the gastrointestinal tract of pigs(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Schweiger, Markus; Steffl, Martin; Amselgruber, Werner M.Zinc is an important co-factor for insulin storage in pancreatic β-cells of different species and the uptake of this ion into insulin containing secretory vesicles is managed by the zinc transporter, ZnT8, a member of the slc30A gene family. Recent studies indicate that this protein is a major autoimmune target in human type 1A diabetes and has also been implicated by genome-wide association studies in type 2 diabetes. Since individuals suffering from type 1 diabetes often develop gastrointestinal motility disorders, we investigated the expression of ZnT8 in the porcine gastrointestinal tract. For this purpose, we studied the cell-type specific expression of ZnT8 in the gut and its co-expression with endocrine hormones that are closely linked to intestinal motility regulation. Nested RT-PCR and immunostaining of sequential serial sections, as well as double-immunostaining using antibodies directed against ZnT8, ghrelin, motilin, neurotensin, serotonin and glucagon-like peptide 1, indicated that ZnT8 is colocalized with ghrelin and motilin. Our findings provide important information about the cell-type specific expression of ZnT8 in the porcine gastrointestinal system. The selective and exclusive expression of ZnT8 in two endocrine cell-types that are engaged in motility functions may be of particular interest for further investigations into type I diabetes-associated gastrointestinal dysfunctions.
- PublicationOpen AccessThe role of high cholesterol-high fructose diet on coronary arteriosclerosis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Swier, Vicki J.; Tang, Lin; Radwan, Mohamed M.; Hunter III, William J.; Agrawa, Devendra K.The effect of fructose in conjunction with high cholesterol diet in the development of atherosclerotic lesions in coronary arteries is not well established. Microswine were fed high cholesterol (HC) or a high cholesterol-high fructose (HCHF) diet containing 18-20% calories from fructose. All swine had high levels of serum cholesterol and non-HDL, thickened intima and accumulation of collagen in the coronaries. Swine fed with HC diet had less stenosis in coronary arteries, lower serum levels of non-HDL, triglycerides, cholesterol, and blood glucose than HCHF group. Coronary lesions in the HC swine were not as progressed as in HCHF and showed low LDL-expressed lipid-laden foam cells. The M1/M2 macrophage phenotype in the HCHF swine differed with the progression of atherosclerosis, with higher density of M1-phenotype in HCHF swine. There was high expression of CCR7 (M1-phenotype) in more advanced lesions in the fibrous cap-like areas, whereas M2- macrophages were abundant in the foam-cell cores. These findings suggest that the addition of a fructose to high cholesterol diet accelerates atherosclerotic lesions in coronary arteries with an increase in M1-macrophages and the propensity to develop features of metabolic syndrome.
- PublicationOpen AccessMRL/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, YasuhiroClarification 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
- PublicationOpen AccessA subset of solitary fibrous tumors express nuclear PAX8 and PAX2: a potential diagnostic pitfall(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) McDaniel, Andrew S.; Palanisamy, Nallasivam; Smith, Steven C.; Robinson, Dan R.; Wu, Yi-Mi; Chinnaiyan, Arul M.; McHugh, Jonathan B.; Greenson, Joel K.; Kunju, Lakshmi P.Solitary fibrous tumor (SFT), a mesenchymal neoplasm with widespread anatomic distribution, can be diagnostically challenging in limited samples. We recently encountered an aspirate of a pancreatic mass, incorrectly interpreted as metastatic renal cell carcinoma based on strong PAX8 expression by immunohistochemistry (IHC). After resection, morphologic features with additional IHC (CD34 positivity) correctly identified this lesion as a SFT. PAX8 and PAX2 are commonly used as renal tumor markers; however, no series has investigated PAX8 or PAX2 expression in SFT. IHC for PAX8 and PAX2 was performed on 41 SFTs (biopsy and resections) from varying sites. Eight were histologically malignant and eight were recurrences of previous resections. PAX8 staining was observed at least focally in 26.8% (11 of 41) SFT cases; additionally, PAX2 was positive in 12.2% (5 of 41 cases) of SFTs. For PAX8 and PAX2 positive cases 45.6% and 40%, respectively, showed diffuse expression. No correlation was found between PAX8/PAX2 positivity and age, tumor size, site, malignancy, or recurrence. In conclusion, a substantial minority of SFTs express PAX8 and PAX2 via IHC. This presents a diagnostic pitfall when evaluating possible metastases from the kidney, particularly when primary tumors show sarcomatoid or spindle cell morphologies.
- PublicationOpen AccessEffect of rehabilitation protocols on muscle function and morphology following hindlimb disuse in weanling rats(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Leite Nogut, Keite i; Bianchi, Eduardo; Chesca Simões, Deise Lúcia; Mattiello-Sverzut, Ana Claudia; de Moura-Jucá, Renata Viana BrígidoBackground: Primary or secondary disorders in developing skeletal muscles are prevalent in physical therapy practice. Assessment of gait functional changes and morphological aspects of hindlimb muscles of weanling rats have not been reported simultaneously in the literature. Rehabilitation by active (eccentric training) and passive (stretching) exercises after hypomobility needs to be investigated. Methods: After ten days of immobilisation in a plantar flexion-shortened position, animals underwent eccentric training on treadmills, intermittent (a single series of ten exercises of 30 seconds each, with a 30-s interval) or continuous stretching protocols for 40 minutes, or had free cage activity for three days. Analysis of gait variables and muscle morphology (immunohistochemical staining of soleus and plantar muscles for fibronectin and types I and III collagen and immunofluorescence staining for dystrophin, laminin, Pax-7, and CD68) were performed. Results: On the third day, the rehabilitated animals touched the ground surface with their toes, except for the group undergoing continuous stretching. The total amount of extracellular macrophages was higher in the rehabilitated animals. The number of satellite cells was not significantly different between groups. Conclusion: Three days of active training (eccentric exercise) showed greater effectiveness compared to the other rehabilitation programs. Weanling rats seem to respond differently to external stimuli such as disuse and remobilisation.
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