更新于：2024-11-01

MMPs x GSDME x CASP family

更新于：2024-11-01

基本信息

关联

项与 MMPs x GSDME x CASP family 相关的药物

WO2023108803

专利挖掘

靶点

CASP family x GSDME x MMPs

作用机制-

在研机构

Cancer Prevention and Treatment Center of Sun Yat sen University (Affiliated Cancer Hospital of Sun Yat sen University, Cancer Research Institute of Sun Yat sen University)

原研机构

Cancer Prevention and Treatment Center of Sun Yat sen University (Affiliated Cancer Hospital of Sun Yat sen University, Cancer Research Institute of Sun Yat sen University)

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MMPs x GSDME x CASP family 相关的临床结果

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100 项与 MMPs x GSDME x CASP family 相关的转化医学

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0 项与 MMPs x GSDME x CASP family 相关的专利（医药）

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项与 MMPs x GSDME x CASP family 相关的文献（医药）

Journal of Translational Medicine

Complement factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis

Article

作者: Ji, Xin ; Zhang, Wen ; Li, Mengtao ; Zhou, Jiaxin ; Feng, Bin ; Fei, Yunyun ; Wu, Xunyao ; Jia, Yimeng ; Tian, Xinping ; Zhao, Lidan

AbstractObjectiveTo explore the role and underlying mechanism of Complement Factor H (CFH) in the peripheral and joint inflammation of RA patients.MethodsThe levels of CFH in the serum and synovial fluid were determined by ELISA. The pyroptosis of monocytes was determined by western blotting and flow cytometry. The inflammation cytokine release was tested by ELISA. The cell migration and invasion ability of fibroblast-like synoviocytes (FLS) were tested by Wound healing Assay and transwell assay, respectively. The potential target of CFH was identified by RNA sequencing.ResultsCFH levels were significantly elevated in the serum and synovial fluid from RA and associated with high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS28). TNF-α could inhibit CFH expression, and CFH combined with TNF-α significantly decreased cell death, cleaved-caspase 3, gasdermin E N-terminal (GSDME-N), and inflammatory cytokines release (IL-1β and IL-6) of RA-derived monocytes. Stimulated with TNF-α increased CFH levels in RA FLS and CFH inhibits the migration, invasion, and TNF-α–induced production of inflammatory mediators, including proinflammatory cytokines (IL-6, IL-8) as well as matrix metalloproteinases (MMPs, MMP1 and MMP3) of RA FLSs. The RNA-seq results showed that CFH treatment induced upregulation of eukaryotic translation initiation factor 3 (EIF3C) in both RA monocytes and FLS. The migration of RA FLSs was promoted and the expressions of IL-6, IL-8, and MMP-3 were enhanced upon EIF3C knockdown under the stimulation of CFH combined with TNF-α.ConclusionIn conclusion, we have unfolded the anti-inflammatory roles of CFH in the peripheral and joints of RA, which might provide a potential therapeutic target for RA patients.

PLOS ONE

TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy

Article

作者: Lange-Sperandio, Bärbel ; Kirschning, Carsten ; Rohling, Jana ; Benz, Marcus R ; Keller, Ursula ; Wyczanska, Maja

Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the kidney; its contribution to renal injury in early life is still a controversial topic. We analyzed TLR2 for a potential role in the neonatal mouse model of congenital obstructive nephropathy. Inborn obstructive nephropathies are a leading cause of end-stage kidney disease in children. Thus, newborn Tlr2-/- and wild type (WT) C57BL/6 mice were subjected to complete unilateral ureteral obstruction (UUO) or sham-operation on the 2nd day of life. The neonatal kidneys were harvested and analyzed at days 7 and 14 of life. Relative expression levels of TLR2, caspase-8, Bcl-2, Bax, GSDMD, GSDME, HMGB1, TNF, galectin-3, α-SMA, MMP-2, and TGF-β proteins were quantified semi-quantitatively by immunoblot analyses. Tubular apoptosis, proliferation, macrophage- and T-cell infiltration, tubular atrophy, and interstitial fibrosis were analyzed immunohistochemically. Neonatal Tlr2-/- mice kidneys exhibited less tubular and interstitial apoptosis as compared to those of WT C57BL/6 mice after UUO. UUO induced neonatally did trigger pyroptosis in kidneys, however to similar degrees in Tlr2-/- and WT mice. Also, tubular atrophy, interstitial fibrosis, tubular proliferation, as well as macrophage and T-cell infiltration were unremarkable. We conclude that while TLR2 mediates apoptosis in the kidneys of neonatal mice subjected to UUO, leukocyte recruitment, interstitial fibrosis, and consequent neonatal obstructive nephropathy might lack a TLR2 involvement.