Structural characterization and mutational assessment of podocin — A novel drug target to nephrotic syndrome — An in silico approach

Tabassum, Asra; Rajeshwari, T.; Soni, Nidhi; Raju, Sree Bhushan; Yadav, Mukesh; Nayarisseri, Anuraj; Jahan, Parveen

doi:10.1007/s12539-014-0190-4

Cited by 22 publications

(13 citation statements)

References 34 publications

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“…The C‐terminus of podocin interacts directly with nephrin to its cytosolic tail domain, where the two proteins oligomerize in lipid rafts to form the filtration slits. Therefore dysregulation in podocin could cause changes in nephrin, which further damages glomerular slit diaphragm functions . Consistent with previous findings, we also observed a significant increase in urinary podocin mRNA expression levels in preeclampsia rats compared to control, indicating compromised slit diaphragm functions.…”

Section: Discussionsupporting

confidence: 91%

“…With this notion in mind, we also examined the urinary levels of both nephrin and podocin. Podocin is a protein of the band‐7‐stomatin family members, and has a transmembrane domain constructing a hairpin conformation . The C‐terminus of podocin interacts directly with nephrin to its cytosolic tail domain, where the two proteins oligomerize in lipid rafts to form the filtration slits.…”

Section: Discussionmentioning

confidence: 99%

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Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor

Gong

Wan

Yuan

et al. 2017

Clin Exp Pharma Physio

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Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an N -nitro-L-arginine methyl ester hydrochloride (L-NAME) induced rat model of preeclampsia. L-NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed. Expressions levels of urinary nephrin and podocin mRNAs were analyzed by RT-PCR. Levels of renal vascular endothelial growth factor (VEGF), renal soluble fms-like tyrosine kinase-1 (sFlt-1) and serum placenta growth factor (PlGF) were also examined. Urine volume, total urine protein and blood pressure were markedly increased in preeclampsia group rats compared to control (P<.05), which were then significantly reduced in preeclampsia+FA group (P<.05). Expressions of urinary nephrin and podocin mRNAs, levels of VEGF, sFlt-1 and PlGF were also reversed in preeclampsia+FA group compared to preeclampsia rats (P<.05). We hereby report for the first time, FA alleviates preeclampsia symptoms in a rat preeclampsia model, supporting its potential value in treating preeclampsia.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor

Gong

Wan

Yuan

et al. 2017

Clin Exp Pharma Physio

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“…Nephrin, a slit diaphragm protein belonging to the immunoglobulin superfamily, is identified as a critical podocyte membrane component, maintaining the barrier function of the glomerular capillary wall [21]. Podocin, a membrane protein of the band-7-stomatin family, is considered to be localized on the membranes of podocyte pedicels, oligomerizes in lipid rafts together with nephrin to form the filtration slits [22]. Recently, it has been revealed that the decreased expression of both nephrin and podocin after podocyte injury, may contribute to the development of proteinuria in MN [23].…”

Section: Discussionmentioning

confidence: 99%

Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway

Wan

Liu

Yang

et al. 2020

BMC Mol and Cell Biol

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Background: PM2.5 is associated closely with an increased risk of membranous nephropathy (MN), however, whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. Triptolide, an active component in Tripterygium wilfordii Hook F, is frequently used to treat MN in China, but its effects on PM2.5-induced podocytes injury is still largely unknown. Therefore, we evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms. Results: Podocytes were incubated with PM2.5 after being pre-treated with triptolide, viability, apoptosis rate and migratory capacity of podocytes were determined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) in podocytes, the cytoskeleton of podocytes, the protein expressions of nephrin, podocin, Bcl-2, Bax, nuclear factor kappa-B/p65 (NF-κB/p65) and phospho-inhibitor of NF-κB (p-IκBα) were measured. Our data showed that PM2.5 treatment significantly increased the disorganization of F-actin stress fibers, the damaged structural integrity of nucleus, the deranged and dissociated cytoskeleton in podocytes, increased the podocytes apoptosis rate, the levels of MDA and LDH, markedly up-regulated the protein expression of Bax, NF-κB/p65 and p-IκBα, downregulated the protein expression of nephrin, podocin and Bcl-2, and significantly decreased the level of SOD, the migration rate and the viability of podocytes, compared with those of the untreated podocytes. These effects of PM2.5 on podocytes, however, were reversed by triptolide administration. Conclusion: These results suggest that triptolide could prevent against PM2.5-induced podocytes injury via suppressing NF-κB signaling pathway.

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“…Information relating to the age, gender, family history, consanguinity was collected from the total cohort and additional information relating to age at disease onset, histopathology and responsiveness to steroid therapy were collected from the patient group. The criterion to distinguish between SRNS and SSNS; and the histopathological variants are given elsewhere [5].…”

Section: Methodsmentioning

confidence: 99%

α-Actinin-4 Gene Mutations, Steroid Responsiveness and FSGS in Adult Onset-Nephrotic Syndrome

Jaffer¹,

Raju²,

Jahan³

2016

Hereditary Genet

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Focal segmental glomerulosclerosis (FSGS) is a common pattern of injury seen in primary as well as secondary renal disorders and is a major cause of steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). SRNS is defined by resistance to standard steroid therapy and it remains one of the most intractable causes of kidney failure. Mutations in α-actinin-4 gene (ACTN4) represent a frequent cause of SRNS associated with an adult onset form of FSGS. We screened a cohort of 374 subjects from the South Indian population for the presence of two missense mutations, K255E and S262P in exon 8 of ACTN4 gene encoding α-actinin-4, an actinfilament crosslinking and bundling protein. Our results revealed that these two mutations were seen only among the patients (4%) in heterozygous form and absent in the controls suggesting that, these mutations were found to be disease causing in nature and the regulation of the actin cytoskeleton of glomerular podocytes may be altered in the patients. Further categorization revealed that K255E and S262P mutations were together responsible for 5% of SRNS and 15% of FSGS cases in our study group. Conversely, these mutations were not found in the controls as well as in the patients with steroid-sensitive nephrotic syndrome (SSNS). This is the first report from India, more studies are warranted to establish the frequency of ACTN4 mutations in our population and such analysis may help in developing mutation(s) specific therapeutic interventions in future.

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Structural characterization and mutational assessment of podocin — A novel drug target to nephrotic syndrome — An in silico approach

Cited by 22 publications

References 34 publications

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor

Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway

α-Actinin-4 Gene Mutations, Steroid Responsiveness and FSGS in Adult Onset-Nephrotic Syndrome

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