Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis

Yang, Lu; Wen, Jun; Chen, Dapeng; Wu, Lingling; Li, QingGang; Xie, Yuansheng; Wu, Di; Liu, Xiaoluan; Chen, Xiangmei

doi:10.1007/s10157-015-1163-6

Cited by 9 publications

(13 citation statements)

References 26 publications

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“…Therefore, HSV was used to establish a murine model of MesPGN. PAS staining results showed the pathological process was consistent with previous reports in which there was a dissolution phenotype during the early stages of modeling, which was followed by mesangial proliferation and mesangial matrix accumulation that returned to normal on day 14 after HSV injection [22]. …”

Section: Discussionsupporting

confidence: 78%

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Gao¹,

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in chemotaxis, cell growth regulation and angiogenesis inhibition. It has been reported that CXCL10 expression is significantly increased in patients with MesPGN (Mesangial proliferative glomerulonephritis). However, the underlying mechanism of CXCL10 in MesPGN reminds unclear. Methods: Wildtype (Cxcl10^+/+) mice and Cxcl10-deficient (Cxcl10^-/-) mice were used to generate a murine model of MesPGN. The histological changes in glomeruli were examined by PAS staining (Periodic Acid-Schiff staining), and cell proliferation was detected by PCNA immunohistochemistry staining. The expression of cell cycle regulatory proteins was analyzed by Western blotting and the effects of CXCL10 on primary mouse renal mesangial cells (MRMC) proliferation were detected using the EDU assay. Furthermore, the specific mechanisms by which CXCL10 affected mesangial cells were investigated in vitro using a specific inhibitor. Results: Typical pathological phenotypes were observed in both mouse types, while the Cxcl10^-/- mice had lighter accumulation of extracellular matrix, less cell proliferation and diminished up-regulation of cell cycle regulatory proteins compared to Cxcl10^+/+ mice at day 7. Furthermore, we observed that CXCL10 inhibition resulted in less activation of ERK phosphorylation, and ERK pathway inhibition by a specific inhibitor, U0126, prevented CXCL10 induced MRMC proliferation and the activation of phosphorylated ERK. Conclusions: CXCL10 may aggravate mesangial proliferation in MesPGN by activating the ERK signaling pathway. These results provide a novel insight into the mechanism and potential therapy target of MesPGN.

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Section: Discussionsupporting

confidence: 78%

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Gao¹,

Wang

et al. 2017

Cell Physiol Biochem

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“…We confirmed that during the process of mesangial proliferation, renal function was damaged due to related pathological changes. The levels of Upro, Scr, and BUN were strongly elevated at the proliferative phase and recovered following it, which indicated that mesangial proliferation injures the glomerular filtration barrier and affects filtration rate, consistent with our earlier study in a mouse MesPGN model [12]. Moreover, we found that serum total protein levels decreased.…”

Section: Discussionsupporting

confidence: 91%

Screening for potential serum biomarkers in rat mesangial proliferative nephritis

et al. 2016

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Mesangial proliferative nephritis (MesPGN) is a common kidney disease worldwide. The main feature of the disease is mesangial cell proliferation-induced injury to kidney function. In this study, we explored serum biomarkers for kidney function injury in anti-Thy1 nephritis. We found that mesangial proliferation were increased on days 5 and 7, and recovered by day 14 in anti-Thy1 nephritis. 24-h urine protein, the ratio of urine protein to urine creatine, serum creatine, and blood urea nitrogen, were increased at days 5 and 7 in the model. We found that TXN, BET1, PrRP, VGF, and NPS differed strongly from controls on days 5 and, associated with kidney injury when detected by SELDI-TOF MS. Moreover, we applied LC-MS to detect differential protein expression and found A2M, C3, ITIH4, ITIH3, VDBP, AFM, and SERPINF2 to be upregulated, and ES1, HPX, SERPINC1, SERPINA1F, SERPINA4, SERPINA3K, SPI, TF, VNN3, SERPINF1, and PON1 to be downregulated, on days 5 and 7, associated with kidney injury. The levels of VNN3 and VDBP were validated by Western blotting. Overall, this study explored a group of candidate biomarkers of mesangial proliferation inducing kidney injury, to provide the basis of an assessment model for MesPGN in the future.

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“…As a molecular marker of proliferation, the Ki67-positive cells in the mesangial area were regarded as mesangial cell proliferation (Lu et al, 2016). The immunohistochemical results showed that Ki67 was obviously exhibited in the glomerulus of model rats, while the Ki67 positive cells numbers were reduced markedly in the normal and treatment groups ( P < 0.01) ( Figures 2A, C ).…”

Section: Resultsmentioning

confidence: 99%

Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway

et al. 2019

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Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney diseases. However, there are no studies reporting the effects of paeoniflorin on MPGN. The present study aims to investigate whether paeoniflorin plays a role in MPGN and confirm the underlying molecular mechanisms. Our results manifested that paeoniflorin strongly restrained 24 h urinary protein and promoted renal function and dyslipidemia in a MPGN rat model. Moreover, paeoniflorin attenuated mesangial cell proliferation and inflammation both in MPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the number of mesangial cells and expressions of proliferation marker Ki67 in MPGN rats. Paeoniflorin also inhibited HMC proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker iNOS were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin was accompanied by a strong inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway. Paeoniflorin enhanced the inhibitory effect of PI3K inhibitor LY294002 and suppressed the activated effect of PI3K agonist insulin-like growth factor 1 (IGF-1) on PI3K/AKT/GSK-3β pathway. In conclusion, these results demonstrated that paeoniflorin ameliorates MPGN by inhibiting mesangial cell proliferation and inflammatory response through the PI3K/AKT/GSK-3β pathway.

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Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis

Cited by 9 publications

References 26 publications

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Screening for potential serum biomarkers in rat mesangial proliferative nephritis

Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway

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