Mechanisms of rapamycin on regulating rat mesangial cell proliferation and cell cycle through mTORC1/p70S6K pathways / 药学学报

To explore the affect and mechanisms of rapamycin on mesangial cell proliferation and cell cycle, rat mesangial cells (HBZY-1) were cultured and divided into the six groups: normal; normal with platelet derived growth factor (PDGF) 20 ng·mL-1; PDGF + rapamycin 1, 10, 100, 1 000 nmol·L-1. The cell proliferation was measured by MTT in 24 and 48 h; flow cytometry was used to detect the cell cycle phase. Western blot was performed to determine cyclin D1,cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), p27, p70S6K/p-p70S6K protein expression. The p27 mRNA was detect by Real-time PCR. The results showed that rapamycin significantly suppressed PDGF induced glomerular mesangial cells (MCs) proliferation in a dose and time-dependent manner, but with the dose increased (1 to 1 000 nmol·L-1), the time dependence gradually weakened. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G0/G1 phase. PDGF at 20 ng·mL-1 significantly increased the expression of cyclin D1, cyclin E and CDK2, CDK4 (P < 0.05), but rapamycin did not affect the expression of cyclin D1, cyclin E and CDK2, CDK4. Rapamycin can significantly inhibited p70S6K phosphorylation, up-regulated the expression of p27 protein and mRNA. Collectively, rapamycin has the effect of inhibiting the glomerular mesangial cells proliferation of mesangial cells by regulating the transcription of p27 mRNA, increasing its protein expression through the mTORC1/p70S6K pathway, resulting in decreased activity of cyclin-CDK, and blocking cell cycle in G0/G1 phase.

Matrix-assisted laser desorption/ionization time of flight mass spectrometry in the genetic basis of systemic lupus erythematosus and the complicating kidney injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is necessary to develop some innovative methods to reveal and discover the novel (SLE)-related protein molecules. In the present study, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was employed to detect the differential expression of serum polypeptides in the patients with systemic lupus erythematosus (SLE) presenting with a family history or complicating with kidney injury so as to identify the proteins associated with the genetic factors and kidney injury in SLE.</p><p><b>METHODS</b>The subjects recruited were divided into four groups, that is, a group of SLE patients with both family history and kidney injury, a group of SLE patients with only kidney injury but no family history, a group of SLE patients with neither family history nor kidney injury, and a control group consisting of healthy volunteers. By adopting MALDI-TOF MS analysis, the serum samples obtained from the three groups of SLE patients were examined and compared with those from the control group; the categorized peptide fingerprint profile was established via the biological data collected from the samples.</p><p><b>RESULTS</b>The expression of protein with a m/z of 4207 Da increased significantly in SLE patients; the protein with a m/z of 2658 Da was expressed in all SLE patients; three proteins (with m/z of 1465, 5332, and 5900 Da respectively) were expressed in the SLE patients complicated with kidney injury and the protein with a m/z of 1943 Da was expressed in SLE patients with family history.</p><p><b>CONCLUSION</b>A number of differential proteins were successfully detected and identified through MALDI-TOF MS detection and these proteins may be associated with the genetic basis of SLE and the complicating kidney injury.</p>

Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.</p><p><b>METHODS</b>Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n = 6) pretreated with normal saline and the LPD group (n = 6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.</p><p><b>RESULTS</b>All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0 ± 12.6) mmHg vs. (284.3 ± 11.3) mmHg at 6 hours after ALI, P < 0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0 ± 0.6) and (2.50 ± 0.08) folds in placebo group; and (2.5 ± 0.5) and (1.40 ± 0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P < 0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg×ml(-1)×g(-1) protein) was significantly lower (P < 0.01) than that in placebo group ((67.2 ± 25.3) pg×ml(-1)×g(-1) protein).</p><p><b>CONCLUSION</b>These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.</p>