RPC6 Up-Regulation in Ang II-Induced Podocyte Apoptosis Might Result from ERK Activation and NF-κB Translocation

Zhang, Han; Ding, Jie; Fan, Qingfeng; Liu, Shufang

doi:10.3181/0901-rm-11

Cited by 73 publications

(62 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 Ang II promoted apoptosis of the cultured rat and mouse podocytes. [18][19][20] However, Ang II-induced apoptosis in human podocytes is not well characterized.…”

mentioning

confidence: 99%

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

Sanchez-Niño

Sanz

Sánchez-López

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

Apoptosis is a driving force of diabetic end-organ damage, including diabetic nephropathy (DN). However, the mechanisms that modulate diabetes-induced cell death are not fully understood. Heat shock protein 27 (HSP27/HSPB1) is a cell stress protein that regulates apoptosis in extrarenal cells and is expressed by podocytes exposed to toxins causing nephrotic syndrome. We investigated the regulation of HSPB1 expression and its function in podocytes exposed to factors contributing to DN, such as high glucose and angiotensin (Ang) II. HSPB1 expression was assessed in renal biopsies from patients with DN, minimal change disease or focal segmental glomerulosclerosis (FSGS), in a rat model of diabetes induced by streptozotocin (STZ) and in Ang II-infused rats. The regulation of HSPB1 was studied in cultured human podocytes and the function of HSPB1 expressed in response to pathophysiologically relevant stimuli was explored by short interfering RNA knockdown. Total kidney HSPB1 mRNA and protein expression was increased in rats with STZ-induced diabetes and in rats infused with Ang II. Upregulation of HSPB1 protein was confirmed in isolated diabetic glomeruli. Immunohistochemistry showed increased glomerular expression of HSPB1 in both models and localized glomerular HSPB1 to podocytes. HSPB1 protein was increased in glomerular podocytes from patients with DN or FSGS. In cultured human podocytes HSPB1 mRNA and protein expression was upregulated by high glucose concentrations and Ang II. High glucose, but not Ang II, promoted podocyte apoptosis. HSPB1 short interfering RNA (siRNA) targeting increased apoptosis in a high-glucose milieu and sensitized to Ang II or TGFb1-induced apoptosis by promoting caspase activation. In conclusion, both high glucose and Ang II contribute to HSPB1 upregulation. HSPB1 upregulation allows podocytes to better withstand an adverse high-glucose or Ang II-rich environment, such as can be found in DN.

show abstract

“…15 Ang II promoted apoptosis of the cultured rat and mouse podocytes. [18][19][20] However, Ang II-induced apoptosis in human podocytes is not well characterized.…”

mentioning

confidence: 99%

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

Sanchez-Niño

Sanz

Sánchez-López

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…The protein level of TRPC6 was found to be markedly increased in response to Ang II stimulation, in parallel with the induced elevation of intracellular Ca 2+ concentration. By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca 2+ influx were inhibited (77). The activation of ERK pathway and subsequent translocation of NF-kappaB also seem to b necessary for the up-regulation TRPC6 induced by Ang II (77).…”

Section: Interaction Of Trpc6 With Other Sd Proteins Of the Filtratiomentioning

confidence: 99%

“…By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca 2+ influx were inhibited (77). The activation of ERK pathway and subsequent translocation of NF-kappaB also seem to b necessary for the up-regulation TRPC6 induced by Ang II (77). Likewise, Nijenhuis and colleagues demonstrated that Ang II regulates TRPC6 mRNA and protein levels in cultured podocytes and that Ang II infusion enhances glomerular TRPC6 expression in vivo.…”

Section: Interaction Of Trpc6 With Other Sd Proteins Of the Filtratiomentioning

confidence: 99%

“…AT1R-EGFR interactions also activate downstream serine/threonine kinases such as the MAPK Regulation of TRPC6 ion channels in podocytes 245 245 pathway in a process that is known to require an increase in cytosolic [Ca 2+ ] (34). Ang II induces membrane ruffling and loss of stress fibers, thereby phenocopying the depletion of synaptopodin or TRPC6 (8,34,47,77).…”

Section: Interaction Of Trpc6 With Other Sd Proteins Of the Filtratiomentioning

confidence: 99%

See 1 more Smart Citation

Regulation of TRPC6 ion channels in podocytes — Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases

Szabó¹,

Ambrus²,

Zákány³

et al. 2015

Acta Physiologica Hungarica

View full text Add to dashboard Cite

The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury.

show abstract

“…1 Recently, a great deal of SD molecules, which relates to podocyte injury have been recognized, including nephrin, podocin, CD2AP, and TRPC6, etc. 2,3 Angiotensin-II (AngII) is an important risk factor in podocyte injury, researchers found it promoted podocyte apoptosis both in vitro and in vivo [4][5][6][7] AngII binds to cell surface G protein-coupled receptors (GPCR), which couple to heterotrimeric G proteins of the Gq/11 family. 8 Gq enhances podocyte apoptosis in a calcineurin (CaN)-dependent fashion, while the activation of CaN could be blocked by CaN inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury

et al. 2015

View full text Add to dashboard Cite

(2015) Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury, Renal Failure, 37:8, 1344-1348 Department of General Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Abstract Context: Podocyte injury is related to increasing proteinuria and contributes to the progression of kidney disease. Calcineurin binding protein 1 (Cabin1) is a repressor of myocyte enhancer factor 2 (MEF2) and calcineurin-mediated transcription in the immune system. Moreover, Cabin1 interacts with p53 and negatively regulates p53 in tumor cells. However, its function in kidney is unknown. Objective: To explore the exact localization of Cabin1 in glomeruli, as well as the relationship between Cabin1 and podocyte injury. Methods: Sprague-Dawley rats were sacrificed to observe the localization and protein expression of Cabin1 in the kidney. Cabin1 localization and protein expression were detected by immunofluorescence staining and western blot, respectively. Mouse podocytes were cultivated at 33 C to propagate, then cells were transferred to an incubator at 37 C to allow differentiation. Differentiated podocytes were stimulated by angiotensin II (AngII) or AngII plus tacrolimus. Cells were harvested to detect the localization and protein expression of Cabin1. Cytoplasmic and nuclear protein were separated by protein extraction kit. Results: Cabin1 mainly localized in the nuclei of glomerular innate cells, it colocalized with WT-1 in podocytes nuclei. Western bolt showed Cabin1 protein remarkably expressed in renal cortex. AngII-induced Cabin1 nuclear protein significantly increased, accompanied by cytoskeleton disruption in cultured mouse podocytes. Conclusion: Cabin1 localizes in glomerular podocytes. AngII induces nuclear translocation of Cabin1 in cultured podocytes.

show abstract

RPC6 Up-Regulation in Ang II-Induced Podocyte Apoptosis Might Result from ERK Activation and NF-κB Translocation

Cited by 73 publications

References 24 publications

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

Regulation of TRPC6 ion channels in podocytes — Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases

Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury

Contact Info

Product

Resources

About