The complement C5b-9 complexes can result in cell apoptosis, but the mechanism of sublytic C5b-9-mediated glomerular mesangial cell (GMC) apoptosis in Thy-1 nephritis (Thy-1N) remains largely unclear. The Gadd45 gene is involved in the cellular response to DNA damage and can promote cell apoptosis. In this study, both Gadd45c expression patterns and pathologic changes of renal tissue were examined in rat Thy-1N. Both Gadd45c expression and GMC apoptosis were significantly decreased in Thy-1N rats upon the depletion of complement with cobra venom factor. Our in vitro studies showed that Gadd45c over-expression increased sublytic C5b-9-induced GMC apoptosis, while Gadd45c gene knockdown by siRNA greatly reduced GMC apoptosis. Moreover, Gadd45c gene silencing in vivo markedly inhibited the pathologic changes in the renal tissue of Thy-1N rats. These data suggest that Gadd45c gene expression is involved in regulating GMC apoptosis mediated by sublytic C5b-9 in Thy-1N.Key words: Apoptosis . Gadd45c . Glomerular mesangial cells . Sublytic C5b-9 .Thy-1 nephritis Supporting Information available online IntroductionMesangioproliferative glomerulonephritis (MsPGN) is a disease with high incidence in humans. Proliferation of glomerular mesangial cells (GMC) in MsPGN appears to be crucial for a subsequent increase in mesangial matrix and development of glomerulosclerosis [1,2]. Rat Thy-1 nephritis (Thy-1N), namely anti-thymocyte serum (ATS) induced nephritis, is a widely used animal model for studying human MsPGN [3,4]. ATS administered in rats binds to Thy-1 antigen on the membrane of GMC and then activates the complement system resulting in immunopathologic injury [5][6][7][8]. Complement activation results in generation of chemotactic factors, such as C5a, and formation of the C5b-9 complex [6,9]. Because GMC damage in Thy-1N is complement-dependent and neutrophil-independent, complement is generally regarded as the principal mediator of GMC lesions in the rats with Thy-1N. Assembly of C5b-9 can result in formation of transmembrane channels or rearrangement of membrane lipid with loss of membrane integrity. However, injury to nucleated cells by C5b-9 is almost non-lytic (sublytic) because the cell surface has many homologous restriction factors such as CD59 and MCP. Sublytic C5b-9 complexes can trigger [4,6,9,10]. Complement deposits are observed in the glomeruli of patients with MsPGN [1,2]. Our previous studies have also revealed the deposition of sublytic C5b-9 complexes on GMC surfaces in Thy-1N rats [9], but the role of sublytic C5b-9 complexes in Thy-1N has not been fully elucidated. During the progression of Thy-1N, GMC undergo two phases of change: early apoptosis/necrosis and secondary proliferation [4,9,11]. The mechanisms governing GMC apoptosis during the early stage of Thy-1N, including the genes involved in GMC apoptosis, remain unclear [12,13]. The growtharrest-and DNA-damage-inducible protein 45 (Gadd45) gene family, which encodes proteins that play important roles in controlling cell growth, has been im...

The proliferation of glomerular mesangial cells (GMCs) and secretion of extracellular matrix (ECM) in rat Thy-1 nephritis (Thy-1N), resembling human mesangioproliferative glomerulonephritis (MsPGN), have been studied for many years, but the mechanisms, especially the role of signalling pathway activation and its regulation in GMCs triggered by sublytic C5b-9 complexes in Thy-1N rats remain largely unclear. In the study, the proliferation of GMCs and production of ECM as well as the role of PI3K/Akt and its regulation, both in GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo), were determined and the results revealed that GMCs proliferation and ECM secretion, both in vitro and in vivo, were notably increased, and that PI3K/Akt1 activation and its regulation, such as TNF receptor-associated factor 6 (TRAF6)-mediated Akt1 ubiquitination and PI3K-dependent Akt1 phosphorylation, were involved in the process of Thy-1N induction. On the other hand, silence of the TRAF6, PI3K or Akt1 genes could obviously diminish the proliferative damages and urinary protein secretion of Thy-1N rats. Together, these data implicated that sublytic C5b-9 complexes in Thy-1N rats could promote GMCs proliferation and ECM production through TRAF6-mediated PI3K-dependent Akt1 activation, in which the ubiquitination and phosphorylation of the Akt1 signal molecule played an important role in the initiation and development of the proliferative changes in the rats with Thy-1N.

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The transplantation of the autologous RPE-Bruch's membrane complex can increase the visual acuity of patients with hemorrhagic AMD. The surviving transplanted graft with functional overlying retina was observed after surgery.

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Obtaining highly valuable Xe from air or other sources is highly important but still seriously restricted by its inherent inert nature and the great difficulty in separation from other inert gases, especially for Xe and Kr that show comparable size. In this work, we show both experimental and theoretical research of how to boost the selective adsorption of Xe over Kr by double-accessible open-metal site in metal–organic framework (MOF). The MOF, namely, UTSA-74, shows a high Xe uptake up to 2.7 mmol/g and a lower Kr uptake of 0.58 mmol/g at 298 K and 1 bar, leading to a high selectivity of 8.4. The effective Xe/Kr separation was further confirmed by both transient breakthrough simulation and experimental breakthrough. The separation mechanism, as unveiled by the grand canonical Monte Carlo simulation and dispersion-corrected density functional theory calculation, is due to the unique double-accessible open-metal site in UTSA-74 that affords stronger interaction toward Xe than Kr.