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10.1172/JCI87037 http://scihub22266oqcxt.onion/10.1172/JCI87037 C4887187!4887187!27183387     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Clin+Invest ä ; 126 (6): 2077-92 Nephropedia Template TP {{tp|p=27183387|t=ä. Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus |pdf=|usr=}}{{27183387}} gab.com Text Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus JO: J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=27183387 #FOAvip Systemic lupus erythematosus (SLE) is a devastating multisystemic autoimmune disorder. However, the molecular mechanisms underlying its pathogenesis remain elusive. Some patients with Noonan syndrome, a congenital disorder predominantly caused by gain-of-function mutations in the protein tyrosine phosphatase SH2 domain?containing PTP (SHP2), have been shown to develop SLE, suggesting a functional correlation between phosphatase activity and systemic autoimmunity. To test this directly, we measured SHP2 activity in spleen lysates isolated from lupus-prone MRL/lpr mice and found it was markedly increased compared with that in control mice. Similar increases in SHP2 activity were seen in peripheral blood mononuclear cells isolated from lupus patients relative to healthy patients. To determine whether SHP2 alters autoimmunity and related immunopathology, we treated MRL/lpr mice with an SHP2 inhibitor and found increased life span, suppressed crescentic glomerulonephritis, reduced spleen size, and diminished skin lesions. SHP2 inhibition also reduced numbers of double-negative T cells, normalized ERK/MAPK signaling, and decreased production of IFN-? and IL-17A/F, 2 cytokines involved in SLE-associated organ damage. Moreover, in cultured human lupus T cells, SHP2 inhibition reduced proliferation and decreased production of IFN-? and IL-17A/F, further implicating SHP2 in lupus-associated immunopathology. Taken together, these data identify SHP2 as a critical regulator of SLE pathogenesis and suggest targeting of its activity as a potent treatment for lupus patients. Twit Text FOAVip Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus ????J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=27183387 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27183387 #FOAvip English Wikipedia <ref>{{Cite pmid|27183387}}</ref> Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus #MMPMID27183387 Wang J; Mizui M; Zeng LF; Bronson R; Finnell M; Terhorst C; Kyttaris VC; Tsokos GC; Zhang ZY; Kontaridis MI J Clin Invest ä[]; 126 (6): 2077-92 PMID27183387show ga Systemic lupus erythematosus (SLE) is a devastating multisystemic autoimmune disorder. However, the molecular mechanisms underlying its pathogenesis remain elusive. Some patients with Noonan syndrome, a congenital disorder predominantly caused by gain-of-function mutations in the protein tyrosine phosphatase SH2 domain?containing PTP (SHP2), have been shown to develop SLE, suggesting a functional correlation between phosphatase activity and systemic autoimmunity. To test this directly, we measured SHP2 activity in spleen lysates isolated from lupus-prone MRL/lpr mice and found it was markedly increased compared with that in control mice. Similar increases in SHP2 activity were seen in peripheral blood mononuclear cells isolated from lupus patients relative to healthy patients. To determine whether SHP2 alters autoimmunity and related immunopathology, we treated MRL/lpr mice with an SHP2 inhibitor and found increased life span, suppressed crescentic glomerulonephritis, reduced spleen size, and diminished skin lesions. SHP2 inhibition also reduced numbers of double-negative T cells, normalized ERK/MAPK signaling, and decreased production of IFN-? and IL-17A/F, 2 cytokines involved in SLE-associated organ damage. Moreover, in cultured human lupus T cells, SHP2 inhibition reduced proliferation and decreased production of IFN-? and IL-17A/F, further implicating SHP2 in lupus-associated immunopathology. Taken together, these data identify SHP2 as a critical regulator of SLE pathogenesis and suggest targeting of its activity as a potent treatment for lupus patients. äInhibition of SHP2 ameliorates the pathogenesis of systemic lupus eryt(epmc).pdf DeepDyve Pubget Overpricing