Browsing by Subject "Renal fibrosis"
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- PublicationOpen AccessExploring the connection between chronic renal fibrosis and bone morphogenic protein-7(Murcia : F. Hernández, 2003) Kalluri, R.; Zeisberg, M.Tubulointerstitial fibrosis is a hallmark feature of chronic renal injury. Specific therapies to control the progression of renal fibrosis towards endstage renal failure are still limited. Transforming growth factor-ß1 (TGF-ß1) has been identified as a major mediator of renal fibrosis. Recent reports have suggested that Bone Morphogenic Protein-7 (BMP-7), another member of the TGF-ß superfamily, accelerates repair of acute renal injury and ameliorates progression of chronic renal fibrosis in a variety of animal models. Interestingly, BMP-7, an endogenous molecule which is present in the normal kidney, vastly decreases its expression during renal injury. Although, the mechanism of BMP-7 action in the kidney is not yet fully understood, the idea of an endogenous molecule with reno-protective function is intriguing
- PublicationRestrictedHypertension and Sex Differences in the Age-Related Renal Changes When Cyclooxygenase-2 Activity Is Reduced During Nephrogenesis(American Heart Association, 2008-12-22) Saez, Fara; Reverte, Virginia; Salazar, Francisco; Llinás, María Teresa; Salazar, F. Javier; Castells Mora, María Teresa; FisiologíaSeveral studies have proposed that cyclooxygenase-2 (COX2) is involved in the regulation of nephrogenesis and that an impaired nephrogenesis may induce the development of hypertension. This study was designed to test the hypothesis that the decrease of COX2 activity leads to a reduction in nephron number, an increase in arterial pressure, and age-dependent renal alterations that are greater in male than in female rats. Arterial pressure was measured from the first to the 16th month of life in rats treated with vehicle or a COX2 inhibitor during the nephrogenic period. Stereological and histological evaluations and renal function studies were performed at different ages. Arterial pressure increased (14%; P<0.05) and nephron number decreased (17%; P<0.05) to similar levels in male and female COX2-treated rats. However, glomerular filtration rate (31%) and renal plasma flow (25%) decreased (P<0.05) in male but not in female COX2-treated rats. A greater (P<0.05) age-dependent elevation in glomerular hypertrophy was also found in male COX2-treated rats compared with their female littermates. Glomerulosclerosis and tubulointerstitial damage in renal cortex and medulla were also significantly enhanced in male but not in female aged COX2-treated rats. Our results demonstrate that the decrease in COX2 activity during renal development leads to a reduction in nephron number and to an elevation in arterial pressure that are similar in males and females. However, the consequent age-dependent deterioration of the renal structure and renal function is only significantly enhanced in male rats.
- PublicationOpen AccessICAM-1 interactions in the renal interstitium: A novel activator of fibroblasts during nephritis(Murcia : F. Hernández, 1999) Clayton, A.; Steadman, R.Chronic renal diseases often degenerate towards end-stage failure, requiring replacement renal therapy. The progressive decline of such diseases is a highly complex, multi-factorial process, which is poorly understood. Indeed, not all chronic conditions take on a progressive course, some may recover to regain normal function, while others may remain functionally impaired yet stable. The structural features of progressive decline, however, show common histological features, despite the diverse nature of the primary injury. These aberrant structural alterations are characterised essentially by a dramatic expansion of the tubulointerstitium, with accompanying tubular atrophy, resulting from interstitial fibrosis. These changes are thought to be a uniform response to prolonged inflammation which may originate in the glomerulus, the vasculature or the interstitial space (Strutz et al., 1995). A histomorphometric analysis of renal diseases, initially performed by Risdon et al. (1968), and supported by Bohle et al. (1987) and others (Eknoyan et al., 1990), revealed that the severity of abnormal glomerular pathology did not always correlate directly with impaired renal function. The extent of interstitial inflammation and the degree of interstitial fibrosis however, were both shown to be more accurate predictors of renal function (Bohle et al., 1992). Furthermore there was a high probability of irreversible functional decline, in the presence of interstitial fibrotic lesions and tubular atrophy. Interstitial fibrosis is therefore considered an important histological marker for end stage renal failure, and is believed to be functionally more significant than primary changes within the glomerulus. In most tissues, resident fibroblasts are believed to be the cells principally responsible for the synthesis and breakdown of extracellular matrix (ECM) within ' connective tissues. Indeed in fibrotic diseases of lung and skin, the resident fibroblast has been identified as the most important cell responsible for the abnormal deposition of ECM components during the disease process (Phan et al., 1985). In the kidney, there are probably several sources of matrix components during fibrosis including tubular epithelia1 cells, inflammatory macrophages (Vaage and Linbland, 1990) as well as interstitial fibroblasts. Although the precise cellular source of the bulk of this matrix requires clarification, there is mounting evidence supporting a significant contribution from resident or infiltrating fibroblasts (Rodemann and Muller, 1990, 1991a,b; Strutz and Muller, 1995).
- PublicationOpen AccessSignificance of α-SMA in myofibroblasts emerging in renal tubulointerstitial fibrosis(F. Hernández y Juan F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Ina, Keisuke; Kitamura, Hirokazu; Tatsukawa, Shuji; Fujikura, YoshihisaMyofibroblast transdifferentiation plays a crucial role in the development and progression of renal tubulointerstitial fibrosis. However, the significance of α-smooth muscle actin (α-SMA) expression, which is the major morphological characteristic of myofibroblasts, remains to be determined in detail. The effect of α-SMA expression on fibrosis tissue was examined by using a fibrosis model (collagen gel) in vitro. The transdifferentiation of fibroblasts into myofibroblasts was triggered in the culture medium with 0.5% fetal bovine serum (FBS)+transforming growth factor (TGF)- ß1, but not with 10% FBS+TGF-ß1. The TGF-ß1- induced gel contraction caused by myofibroblasts was greater than that by fibroblasts. Gel contraction by myofibroblasts involved the Ca2+-dependent myosin light chain kinase pathway, as well as the activation of Rho kinase and p38 mitogen-activated protein kinase (MAPK). Taken together, these findings suggest that α- SMA expression in renal interstitial fibroblasts, i.e., myofibroblast transdifferentiation, accelerates the contraction of the tubulointerstitial fibrosis tissue via the Ca2+-dependent pathway, in addition to the pathways involved in fibroblast contraction; this event may lead to renal atrophy and renal failure.
- PublicationOpen AccessTripartite motif-containing 35 (TRIM35) is up-regulated in UUO-induced renal fibrosis animal model(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Chen, Yu; Ding, Yue; Wang, Li-MingRenal fibrosis has been recognized as a serious health threat in the world because of the high cost of treatment and poor prognosis. However, the molecular mechanism of renal fibrosis is still largely unknown. In this study, we aimed at illustrating the role of TRIM35 in the renal fibrosis process. A UUO mouse model and a TGF-β1-induced tubulointerstitial fibrosis model were constructed for the research of renal fibrosis at animal and cell level, respectively. Hematoxylin-eosin and Masson staining were used for visualizing the pathological change. qRT-PCR, Western blot analysis and immunohistochemical staining were used to detect the expression of fibrosis-associated proteins and TRIM35. The results showed that, after the modeling, the expressions of α-SMA, Collagen I, Collagen III, Fibronectin and Snail1 were up-regulated, while the expression of E-cadherin was down-regulated, indicating the successful construction of animal and cell models. More importantly, TRIM35 was proved to be upregulated in both animal and cell models. Therefore, this study demonstrates the potential promotional effect of TRIM35 in the renal fibrosis process, which may prove to be a new biomarker for the diagnosis and development of new treatments of renal fibrosis.
- PublicationOpen AccessUpregulation of miRNA-1228-3p alleviates TGF-β-induced fibrosis in renal tubular epithelial cells(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Shen, Huajuan; He, Qiang; Dong, Yongze; Shao, Lina; Liu, Yueming; Gong, JianguangBackground. Chronic kidney disease (CKD) has become a major public health issue, which can lead to renal fibrosis regardless of the initial injury. It has been previously reported that miRNA-1228-3p was correlate with the progression of kidney fibrosis. However, the mechanism by which miRNA-1228-3p regulates renal fibrosis remains unclear. Methods. Renal tubular epithelial cells (HK-2) were treated with TGF-β1 (10 ng/ml) in an in vitro model of renal fibrosis. Gene and protein expressions in HK-2 cells were measured by Western-blot and RT-qPCR, respectively. The relation between miRNA-1228-3p and its target gene was investigated by dual luciferase report analysis. Results. Upregulation of miRNA-1228-3p significantly inhibited TGF-β1-induced fibrosis of HK-2 cells in vitro by targeting GDF11. In addition, miRNA-1228-3p exhibited anti-fibrosis effect through inhibition of the smad2/smad4 signaling pathway. Conclusion. Upregulation of miRNA-1228-3p markedly inhibited the progression of renal fibrosis in vitro, indicating that miRNA-1228-3p may serve as a potential novel target for the treatment of renal fibrosis