Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurren...Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.展开更多
Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The differ...Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.展开更多
OBJECTIVE:To explore the underlying molecular mechanism of Phellinus linteus(P.linteus).METHODS:We used a tandem mass tag-based quantitative proteomic method to determine the differentially expressed proteins.Network ...OBJECTIVE:To explore the underlying molecular mechanism of Phellinus linteus(P.linteus).METHODS:We used a tandem mass tag-based quantitative proteomic method to determine the differentially expressed proteins.Network pharmacology analysis was used to analysis the main components of P.linteus and construct the compound-target network.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were used to validate the analyses results.RESULTS:The expression levels of thrombospondin-1(TSP-1)and transforming growth factor(TGF)-β1/Smad3 signaling pathway proteins were significantly upregulated in focal segmental glomeruloscleosis(FSGS)rats.The P.linteus reduced the expression levels of TSP-1 and TGF-β1 signaling pathway proteins.Network pharmacology analysis revealed that protocatechualdehyde was the main active component.Subsequent in vivo and in vitro experiments validated the results of proteomic and network pharmacology analyses.CONCLUSIONS:Our results suggested that P.linteus may inhibit renal sclerosis by inhibiting TSP-1-activated TGF-β1 signaling and may have potential applications in the treatment of FSGS.展开更多
文摘Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.
文摘Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.
基金Public Welfare Technology Application Research Program of Zhejiang Province:Study on the Application of Phellinus linteus Protocatechualdehyde in Inhibiting Glomerular Extracellular Matrix Accumulation based on TSP-1 Double Luciferase Reporting System(No.LGC21H290002)Key Projects of Zhejiang Administration of Traditional Chinese Medicine:Quality and Safety Evaluation of Cultivated Phellinus linteus in Zhejiang Province and its Comprehensive Application in the Prevention and Treatment of Kidney Disease(No.2020ZZ016)。
文摘OBJECTIVE:To explore the underlying molecular mechanism of Phellinus linteus(P.linteus).METHODS:We used a tandem mass tag-based quantitative proteomic method to determine the differentially expressed proteins.Network pharmacology analysis was used to analysis the main components of P.linteus and construct the compound-target network.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were used to validate the analyses results.RESULTS:The expression levels of thrombospondin-1(TSP-1)and transforming growth factor(TGF)-β1/Smad3 signaling pathway proteins were significantly upregulated in focal segmental glomeruloscleosis(FSGS)rats.The P.linteus reduced the expression levels of TSP-1 and TGF-β1 signaling pathway proteins.Network pharmacology analysis revealed that protocatechualdehyde was the main active component.Subsequent in vivo and in vitro experiments validated the results of proteomic and network pharmacology analyses.CONCLUSIONS:Our results suggested that P.linteus may inhibit renal sclerosis by inhibiting TSP-1-activated TGF-β1 signaling and may have potential applications in the treatment of FSGS.
