Background
Toll-like receptors (TLRs) are critical sensors for the conservation of bacterial molecules and play a key role in host defense against pathogens. The effect of TLRs on the maintenance of diabetic nephropathy (DN) and resistance to infection has been investigated; however, the detailed effects of TLR9 on DN development remain elusive.
Methods
We performed quantitative reverse transcription-polymerase chain reaction and western blotting to detect TLR9 expression levels in the kidneys of experimental mice (db/db) and high-glucose-treated mouse mesangial cell strains (MCs).
Results
TLR9 expression was found to be remarkably upregulated in the kidneys of experimental mice (db/db) and MCs cultivated under hyperglycemic conditions. Moreover, knockdown of TLR9 could restrain NF-kB viability and downregulate the NLRP3 inflammasome in high glucose-treated MCs. TLR9 inhibition also alleviated inflammation and apoptosis, which was reversed by the addition of the NF-κB activator, betulinic acid. Furthermore, depleted TLR9 levels restrained NF-κB viability and NLRP3 expression and reduced kidney inflammation, microalbuminuria discharge, blood sugar level, and glomerular damage in experimental mice (db/db) kidneys.
Conclusions
These findings offer novel insights into the regulation of TLR9 via the nuclear factor-kB/NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome inflammation pathways in DN progression.
BackgroundProteinuria is an indicator of subsequent renal function decline in most nephropathies and early proteinuria has been assumed to be a risk factor of poor kidney transplant outcomes. However, there is no information about the effect of earlier-proteinuria at the first week on short-term graft function after living donor renal transplantation.MethodsRetrospective cohort study of 439 living donor kidney transplants to analyze the effect of early proteinuria at 7-day post-transplantation on short-term prognosis of living donor renal transplantation. Patients were stratified into 2 groups according to the definition of earlier-proteinuria: Group A as proteinuria < 0.4 g/24h and Group B as proteinuria ≥ 0.4 g/24h, and differences over the first year post-transplantation were analyzed.ResultsPatients with earlier-proteinuria ≥ 0.4 g/24h had a significantly higher 1-year proteinuria and lower 1-year graft function post-transplantation. Discrepancies of weight ratio of donor-recipient and mean artery pressure difference of recipient to donor influenced the urine protein excretion at the 7-day post-transplantation.ConclusionsEarlier-proteinuria at 7-day after living donor renal transplantation was associated with short-term graft function. To eliminate the functional discrepancies between living donors and recipients could be viewed as a solution of reducing earlier-proteinuria.
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