Ezrin Is Down-Regulated in Diabetic Kidney Glomeruli and Regulates Actin Reorganization and Glucose Uptake via GLUT1 in Cultured Podocytes

Wasik, Anita A.; Koskelainen, Susanna; Hyvönen, Mervi E.; Musante, Luca; Lehtonen, Eero; Koskenniemi, Kerttu; Tienari, Jukka; Vaheri, Antti; Kerjaschki, Dontscho; Szalay, Csaba Imre; Révész, Csaba; Varmanen, Pekka; Nyman, Tuula A.; Hamar, Péter; Holthöfer, Harry

doi:10.1016/j.ajpath.2014.03.002

Cited by 32 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in podocyte structure are an early feature of diabetic nephropathy. A recent paper showed down‐regulation of ezrin in glomerular extracts from streptozotocin‐induced diabetic rats, and our finding that AGEs reduced ezrin levels in human podocytes suggests that AGEs could mediate this effect. Podocytes actively take up AGE‐BSA with significantly higher levels of the AGEs pentosidine and carboxymethyllysine in cells grown in AGE‐BSA for 24 h compared with those grown in BSA .…”

Section: Discussionsupporting

confidence: 75%

“…NHERF2 and podocalyxin, which are components of ezrin complexes, are also down‐regulated in glomeruli from diabetic rats . Partial ezrin knockdown in podocytes using siRNA caused actin rearrangement to increase cortical actin and alter glucose uptake . In the present study, AGE‐BSA treatment resulted in more rounded podocytes with fewer protrusions which is indicative of more cortical actin rather than long actin stress fibres.…”

Section: Discussionsupporting

confidence: 50%

“…In rats, puromycin disrupts podocalyxin/ezrin/NHERF2/actin complexes, perturbs foot process organization and causes severe, nephrotic‐range proteinuria . NHERF2 and podocalyxin, which are components of ezrin complexes, are also down‐regulated in glomeruli from diabetic rats . Partial ezrin knockdown in podocytes using siRNA caused actin rearrangement to increase cortical actin and alter glucose uptake .…”

Section: Discussionmentioning

confidence: 99%

“…Ezrin has multiple functions in podocytes, as CLIC 5A and sphingolipid 1 phosphatase have recently also been shown to interact with ezrin, while a role for ezrin in glucose transport has also been described in podocytes . The significance of these interactions for kidney and podocyte function is as yet unknown.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Ezrin contributes to impaired podocyte migration and adhesion caused by advanced glycation end products

McRobert

Bach

2015

Nephrology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Ezrin contributes to impaired podocyte migration and adhesion caused by advanced glycation end products

McRobert

Bach

2015

Nephrology

View full text Add to dashboard Cite

show abstract

“…Thus, glucose increased the collapse of podocyte foot process due to the reduced interaction between plasma membrane and actin cytoskeleton. One investigation shows that ezrin is downregulated in diabetic glomeruli and controls actin reorganization in cultured podocytes . In this study, the glucose load reduced the induction of cortactin and Arp2/3 in podocytes.…”

Section: Discussionsupporting

confidence: 56%

Eucalyptol Ameliorates Dysfunction of Actin Cytoskeleton Formation and Focal Adhesion Assembly in Glucose‐Loaded Podocytes and Diabetic Kidney

Kim

Kang

Kim

et al. 2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Podocytes are a component of glomerular filtration barrier with interdigitating foot processes. The podocyte function depends on the dynamics of actin cytoskeletal and focal adhesion crucial for foot process structure. This study investigates the renoprotective effects of eucalyptol on the F‐actin cytoskeleton formation and focal adhesion assembly in glucose‐loaded podocytes and diabetic kidneys. Methods and results Eucalyptol at 1–20 µm reverses the reduction of cellular level of F‐actin, ezrin, cortactin, and Arp2/3 in 33 mm glucose‐loaded mouse podocytes, and oral administration of 10 mg kg–1 eucalyptol elevates tissue levels of actin cytoskeletal proteins reduced in db/db mouse kidneys. Eucalyptol inhibits podocyte morphological changes, showing F‐actin cytoskeleton formation in cortical regions and agminated F‐actin along the cell periphery. Eucalyptol induces focal adhesion proteins of paxillin, vinculin, talin1, FAK, and Src in glucose‐exposed podocytes and diabetic kidneys. Additionally, GTP‐binding Rac1, Cdc42, Rho A, and ROCK are upregulated in glucose‐stimulated podocytes and diabetic kidneys, which is attenuated by supplying eucalyptol. Rho A gene depletion partially diminishes GSK3β induction of podocytes by glucose. Conclusion Eucalyptol ameliorates F‐actin cytoskeleton formation and focal adhesion assembly through blockade of the Rho signaling pathway, entailing partial involvement of GSK3β, which may inhibit barrier dysfunction of podocytes and resultant proteinuria.

show abstract

Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis

Caster

Korte

Merchant

et al. 2015

Proteomics Clinical Apps

View full text Add to dashboard Cite

PURPOSE Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. EXPERIMENTAL DESIGN Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. RESULTS LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36-50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. CONCLUSION AND CLINICAL RELEVANCE Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers.

show abstract

Ezrin Is Down-Regulated in Diabetic Kidney Glomeruli and Regulates Actin Reorganization and Glucose Uptake via GLUT1 in Cultured Podocytes

Cited by 32 publications

References 41 publications

Ezrin contributes to impaired podocyte migration and adhesion caused by advanced glycation end products

Ezrin contributes to impaired podocyte migration and adhesion caused by advanced glycation end products

Eucalyptol Ameliorates Dysfunction of Actin Cytoskeleton Formation and Focal Adhesion Assembly in Glucose‐Loaded Podocytes and Diabetic Kidney

Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis

Contact Info

Product

Resources

About