RESUMO
Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis and its pathogenesis is associated with the activity of mesenchymal cells (fibroblasts), being essentially characterized by a process of excessive accumulation resulting from the deposition of extracellular matrix components. The aim of this study was to characterize the morphological presentation of chronic and fibrotic lesions in the glomerular, tubular, interstitial, and vascular compartments in feline CKD, as well as the possible participation of myofibroblasts in renal fibrotic processes in this species. Cat kidneys were collected and processed according to the conventional techniques for light microscopy, circular polarization, immunohistochemistry, and electron microscopy. Fibrotic alterations were present in all compartments analyzed. The main findings in the glomerular compartment were different degrees of glomerular sclerosis, synechia formation, Bowman's capsule calcification, in addition to glomerular basement membrane thickening and pericapsular fibrosis. The tubulointerstitial compartment had intense tubular degeneration and the immunostaining in tubular cells for mesenchymal cell markers demonstrated the possibility of mesenchymal epithelial transition and consequent involvement of myofibroblasts in the development of interstitial tubule damage. Infiltration of inflammatory cells, added to vessel thickening and fibrosis, demonstrated the severity and role of inflammation in the development and perpetuation of damage. Thus, we may conclude that fibrotic lesions play a relevant role in feline CKD and the mechanism of perpetuation of these lesions need further elucidation regarding the origin and participation of myofibroblasts and consequent mesenchymal epithelial transition in this species.
Assuntos
Doenças do Gato/patologia , Rim/patologia , Insuficiência Renal Crônica/veterinária , Actinas/ultraestrutura , Animais , Gatos , Colágeno/ultraestrutura , Matriz Extracelular/ultraestrutura , Feminino , Fibroblastos/ultraestrutura , Fibrose/veterinária , Imuno-Histoquímica/métodos , Imuno-Histoquímica/veterinária , Inflamação/veterinária , Rim/ultraestrutura , Glomérulos Renais/patologia , Glomérulos Renais/ultraestrutura , Masculino , Microscopia/métodos , Microscopia/veterinária , Microscopia Confocal/veterinária , Microscopia Eletrônica/veterinária , Microscopia de Polarização/veterinária , Miofibroblastos/ultraestrutura , Insuficiência Renal Crônica/patologiaRESUMO
Chronic kidney disease (CKD) is a relevant disease in feline clinic. The tubulointerstitial damage, with collagen deposition and fibrosis, is an important result of this process. The aim of this study was to quantify and correlate the deposition of collagen and severity of interstitial fibrosis (IF) in the kidney from cats in different stages of CKD. Kidney fragments from 10 adult cats with CKD were analyzed and stained by Masson's trichrome (MT) and Picrosirius red (PSR) for circular polarized microscopy. Random quantitative analysis was performed on MT sections to classify the degree of IF, per field area, with and without circular polarization. Statistics correlations were performed by Spearman's (ρ; p < .05). There was a significant correlation of IF quantification with the area of interstitial collagen deposition by polarized PSR (PSRp) (r = .7939, p = .0098) and nonpolarized PSR (PSRn) (r = .7781, p = .0080). There was a positive correlation of serum creatinine (sCr) at different stages of CKD with PSRp (r = .7939, p = .0098), PSRn (r = .8667, p = .0027) and MT (r = .7818, p = .0117). Correlations between the percentage of quantified area was also positive from PSRp to PSRn (r = .9030, p = .0009) and PSRp to MT (r = .7939, p = .0098). The PSRN was also correlated with MT (r = .9273, p = .0001). The correlation with IF and sCr follows the disease evolution and the quantification of collagen by PSR is an excellent tool for analyzing the disease severity at different stages.
Assuntos
Compostos Azo/química , Doenças do Gato/patologia , Colágeno/análise , Corantes/química , Microscopia de Polarização/métodos , Insuficiência Renal Crônica/veterinária , Animais , Doenças do Gato/diagnóstico , Gatos , Colágeno/ultraestrutura , Creatinina/sangue , Feminino , Fibrose , Rim/química , Rim/patologia , Rim/ultraestrutura , Masculino , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/patologia , Índice de Gravidade de DoençaRESUMO
In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular zone (SVZ) and subgranular zone (SGZ) are the main neurogenic regions in the adult brain. Therein, resides a subpopulation of astrocytes that act as neural stem cells (NSCs). Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of NSCs. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of NSCs and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult NSCs under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells.