Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice

Moon, Jae Seung; Mun, Chin Hee; Kim, Jung Ho; Cho, Jen Young; Park, Sung Dong; Park, Tae Yoon; Shin, Jae Ho; Ho, Chun Chang; Park, Yong Bum; Ghosh, Sankar; Bothwell, Alfred L.M.; Lee, Sang Won; Lee, Sang Kyou

doi:10.1016/j.kint.2017.11.017

Cited by 7 publications

(11 citation statements)

References 36 publications

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“…Anti-dsDNA is the most critical and pathogenic autoantibody in nephritis in NZB/W F1 mice [ 26 , 27 ], and anti-dsDNA may reflect nephritis severity in NZB/W F1 mice [ 28 , 29 ]. MPL and 3 and 1 mg/kg PCG-treated mice exhibited significant reductions in the serum concentration of anti-dsDNA compared to that in vehicle-treated mice (67.5%, 52.1%, and 48.1%, respectively) ( Figure 6 A).…”

Section: Resultsmentioning

confidence: 99%

“…Second, mycophenolate mofetil may be administered together with glucocorticoids owing to its lower toxicity than that of cyclophosphamide. In addition, glucocorticoid monotherapy and combination therapy with high-dose glucocorticoids and mycophenolate mofetil showed no significant difference in therapeutic efficacy [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Among various autoantibodies that can form immune complexes and are deposited in kidneys, anti-dsDNA is the most important for LN pathogenesis [ 26 , 27 , 28 ]. Thus, reducing the serum concentration of anti-dsDNA may prevent LN development and aggravation.…”

Section: Discussionmentioning

confidence: 99%

“…Proteinuria was measured twice per week using albumin reagent strips for spot urine (Yongdong Pharmaceutical Co., Yongin, Korea). The amount of proteinuria was determined by the following semi-quantitative scoring system: 0 = none or trace; 1+, ≤00 mg/dL; 2+, ≤300 mg/dL; 3+, ≤1000 mg/dL; 4+, ≥1000 mg/dL [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

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Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

Seo

Mun

Park

et al. 2020

IJMS

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Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

Seo

Mun

Park

et al. 2020

IJMS

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“…This is a relevant finding in the context of several autoimmune diseases that are driven by both abnormalities in the innate and adaptive immune arms, such as SLE. Th1 cells have been described to play important roles in SLE and in lupus-associated organ damage such as lupus nephritis (55,56). Therefore, targeting Th1 cells by PAD inhibition may add a beneficial protective effect in SLE.…”

Section: Discussionmentioning

confidence: 99%