Transcriptome Analysis of the Response of Cultured Murine Podocytes to Puromycin Aminonucleoside

Kang, Hae‐Eun; Paik, Kyung Hoon; Cho, H.Y.; Lee, B.H.; Ha, Il‐Soo; Choi, Yong; Cheong, Hae Il

doi:10.1159/000286518

Cited by 4 publications

(2 citation statements)

References 44 publications

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“…Podocin is encoded by NPSH2 gene and is a new member of the stomatin family of lipid raft-associated proteins. Podocin functions as a supporting protein in the maintenance of the podocyte process and integrity of SD [11]. Other proteins, including Neph1, FAT-1 [12], ZO-1 [13], and podocalyxin [14], are noted in animal mutant models, and mutations of any of these proteins result in massive proteinuria and early postnatal death.…”

Section: Introductionmentioning

confidence: 99%

Yi Qi Qing Re Gao Attenuates Podocyte Injury and Inhibits Vascular Endothelial Growth Factor Overexpression in Puromycin Aminonucleoside Rat Model

Zhan

Yang

Wen

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Proteinuria is the hallmark of chronic kidney disease. Podocyte damage underlies the formation of proteinuria, and vascular endothelial growth factor (VEGF) functions as an autocrine/paracrine regulator. Yi Qi Qing Re Gao (YQQRG) has been used to treat proteinuria for more than two decades. The objective of this study was to investigate the protective effect and possible mechanisms of YQQRG on puromycin aminonucleoside (PAN) rat model. Eighty male Sprague-Dawley rats were randomized into sham group, PAN group, PAN + YQQRG group, and PAN + fosinopril group. Treatments were started 7 days before induction of nephrosis (a single intravenous injection of 40 mg/kg PAN) until day 15. 24 h urinary samples were collected on days 5, 9, and 14. The animals were sacrificed on days 3, 10, and 15, respectively. Blood samples and renal tissues were obtained for detection of biochemical and molecular biological parameters. YQQRG significantly reduced proteinuria, elevated serum albumin, and alleviated renal pathological lesions. YQQRG inhibited VEGF-A, nephrin, podocin, and CD2AP mRNA expression and elevated nephrin, podocin, and CD2AP protein levels starting on day 3. In conclusion, YQQRG attenuates podocyte injury in the rat PAN model through downregulation of VEGF-A and restoration of nephrin, podocin, and CD2AP protein expression.

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Section: Introductionmentioning

confidence: 99%

Yi Qi Qing Re Gao Attenuates Podocyte Injury and Inhibits Vascular Endothelial Growth Factor Overexpression in Puromycin Aminonucleoside Rat Model

Zhan

Yang

Wen

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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“…Podocin is a member of the band‐7‐stomatin protein family of lipid raft‐associated proteins, which interacts with the adapter protein CD2‐associated protein (CD2AP). Podocin functions as a supporting protein in the maintenance of the podocyte process and slit diaphragm integrity (16). CD2AP functions as a gatekeeper for reorganization of the podocyte microfilament system and consequent proteinuria (17).…”

mentioning

confidence: 99%

Lack of serum‐ and glucocorticoid‐inducible kinase 3 leads to podocyte dysfunction

et al. 2018

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Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)-mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN. Adriamycin (ADR)-treated mice developed proteinuria and had decreased renal glomerular SGK3 expression in comparison to control mice. Consistent with a role for SGK3 in the ADR effect, SGK3 knockout (KO) mice had markedly reduced kidney podocin expression and significantly elevated proteinuria compared with wild-type mice. Electron microscopy revealed that SGK3 KO mice displayed partial effacement of podocyte foot processes. Further, a SGK3 target protein, glycogen synthase kinase-3 (GSK3), was discovered to be dramatically activated in PAN and SGK3 shRNA-treated MPCs and in SGK3 KO mice. Taken together, these data strongly suggest that SGK3 plays a significant role in regulating podocyte function, likely by controlling the expression and activity of GSK3.-Peng, L.-Q., Zhao, H., Liu, S., Yuan, Y.-P., Yuan, C.-Y., Mwamunyi, M.-J., Pearce, D., Yao, L.-J. Lack of serum- and glucocorticoid-inducible kinase 3 leads to podocyte dysfunction.

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Protosappanin‐A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT‐mTOR signaling

Zheng¹,

Zhang

Chen

et al. 2019

Cell Biology International

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Protosappanin‐A (PrA) and oleanolic acid (OA), which are important effective ingredients isolated from Caesalpinia sappan L., exhibit therapeutic potential in multiple diseases. This study focused on exploring the mechanisms of PrA and OA function in podocyte injury. An in vitro model of podocyte injury was induced by the sC5b‐9 complex and assays such as cell viability, apoptosis, immunofluorescence, quantitative real‐time polymerase chain reaction, and western blot were performed to further investigate the effects and mechanisms of PrA and OA in podocyte injury. The models of podocyte injury were verified to be successful as seen through significantly decreased levels of nephrin, podocin, and CD2AP and increased level of desmin. The sC5b‐9‐induced podocyte apoptosis was inhibited in injured podocytes treated with PrA and OA, accompanied by increased protein levels of nephrin, podocin, CD2AP, and Bcl2 and decreased levels of desmin and Bax. The p‐AKT/p‐mTOR levels were also reduced by treatment of PrA and OA while AKT/mTOR was unaltered. Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K‐AKT inhibitor). PrA and OA were also seen to inhibit podocyte apoptosis and p‐AKT/p‐mTOR levels induced by IGF‐1 (a PI3K‐AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT‐mTOR signaling.

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Transcriptome Analysis of the Response of Cultured Murine Podocytes to Puromycin Aminonucleoside

Cited by 4 publications

References 44 publications

Yi Qi Qing Re Gao Attenuates Podocyte Injury and Inhibits Vascular Endothelial Growth Factor Overexpression in Puromycin Aminonucleoside Rat Model

Yi Qi Qing Re Gao Attenuates Podocyte Injury and Inhibits Vascular Endothelial Growth Factor Overexpression in Puromycin Aminonucleoside Rat Model

Lack of serum‐ and glucocorticoid‐inducible kinase 3 leads to podocyte dysfunction

Protosappanin‐A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT‐mTOR signaling

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