期刊论文详细信息
Diagnostic Pathology
Podocin and Beta Dystroglycan expression to study Podocyte-Podocyte and basement membrane matrix connections in adult protienuric states
Vinay Sakhuja1  Charan Singh Rayat2  Ashwani Kumar2  Kusum Joshi2  Ritambhra Nada2  Praveen B Shankar2 
[1] Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India;Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
关键词: Podocin;    Minimal change disease;    Membranous glomerulonephritis;    IgA nephropathy;    Focal segmental glomerulosclerosis;    Beta dystroglycan;   
Others  :  802894
DOI  :  10.1186/1746-1596-9-40
 received in 2013-10-14, accepted in 2014-01-19,  发布年份 2014
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【 摘 要 】

Background

Podocytes can be the primary site of injury or secondarily involved in various protienuric states. Cross talk between adjacent foot processes and with basement membrane is important for slit diaphragm function. Does expression of podocyte associated proteins in kidney biopsies alter with site/type of primary injury? Genetic mutations of podocin result in steroid resistant FSGS. Can protein expression of podocin predict resistant cases to initiate further genetic evaluation?

Methods

Adult patients (n-88) with protienuria- minimal change disease(MCD)-22, focal segmental glomerulosclerosis(FSGS)-21,membranous glomerulonephritis(MGN)-25 and IgA nephropathy(IgAN)-20 were selected for immunohistochemistry with podocin and beta dystroglycan . Results were graded (0 - 3+scale )and compared with control biopsies and internal control. Treatment and follow up (6 months -2 ½ years) of FSGS and MCD cases were collected.

Results

There was intense to moderate staining of the podocytes with podocin and β dystroglycan in the glomeruli in all cases (MCD, FSGS, IgAN and MGN) except for weak staining with β dystroglycan in 3 cases of MCD. There was loss of immunostains in areas of segmental/global sclerosis. There was no significant difference in the staining pattern between the groups. In primary podocytopathies, staining pattern did not differ between steroid resistant, sensitive or dependent cases.

Conclusions

Immunohistochemical expression of podocin and β dystroglycan does not differ in nephropathies which have different site of injury depending on absence (MCD and FSGS) or presence of immune deposits and their localization (MGN and IgAN). Podocin and β dystroglycan staining did not differentiate steroid sensitive and resistant cases, hence, does not give clue to initiate genetic studies. However, analysis of bigger cohort may be required.

Summary

Podocin and β dystroglycan immunohistochemistry was done to analyze podocyte - podocyte and podocyte -basement membrane matrix connections in adult protienuric states. Primary podocytopathies i.e. MCD and FSGS and secondary podocytopathy due to immune complex deposition i.e. MGN (subepithelial) and IgAN (mesangial) were analyzed. There was no difference in staining patterns between primary and secondary podocytopathies or between steroid sensitive, resistant and dependent cases of FSGS and MCD.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2258608781052786 webcite

【 授权许可】

   
2014 Shankar et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Pollak MR: Inherited Podocytopathies: FSGS and Nephrotic Syndrome from a Genetic Viewpoint. J Am Soc Nephrol 2002, 13:3016-3023.
  • [2]Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, D'Agati V, Appel G: Adult Minimal-Change Disease: Clinical Characteristics, Treatment, and Outcomes. Clin J Am Soc Nephrol 2007, 2:445-453.
  • [3]Skoberne A, Konieczny A, Schiffer M: Glomerular epithelial cells in the urine: what has to be done to make them worthwhile? Am J Physiol Renal Physiol 2008, 296:230-241.
  • [4]Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Ebihara I, Koide H: The urinary pododcyte as a marker for the differential diagnosis of idiopathic focal segmental glomerulosclerosis and minimal change nephrotic syndrome. Am J Nephrol 2000, 20:175-179.
  • [5]Regele Hm FE, Langer B, Poczewki H, Kraxberger I, Bittner Re, Kerjaschki D: Glomerular Expression of Dystroglycans Is Reduced in Minimal Change Nephrosis But Not in Focal Segmental Glomerulosclerosis. J Am Soc Nephrol 2000, 11:403-412.
  • [6]Vogtländer NP, Van der Vlag J, Bakker MA, Dijkman HB, Wevers RA, Campbell KP, Wetzels JF, Berden JH: Expression of sialidase and dystroglycan in human glomerular diseases. Nephrol Dial Transplant 2010, 25:478-484.
  • [7]Giannico G, Yang H, Neilson EG, Fogo AB: Dystroglycan in the Diagnosis of FSGS. Cin J Am Soc Nephrol 2009, 4:1747-1753.
  • [8]Schmid H, Henger A, Cohen CD, Frach K, Gröne H-J, Schlöndorff D, Kretzler M: Gene Expression Profiles of Podocyte-Associated Molecules as Diagnostic Markers in Acquired Proteinuric Diseases. J Am Soc Nephrol 2003, 14:2958-2966.
  • [9]Koop K, Eikmans M, Baelde HJ, Kawachi H, de Heer E, Paul LC, Bruijn JA: Expression of Podocyte-Associated Molecules in Acquired Human Kidney Diseases. J Am Soc Nephrol 2003, 14:2063-2071.
  • [10]Horinouchi I, Nakazato H, Kawano T, Iyama K-i, Furuse A, Arizono K, Machida J, Sakamoto T, Endo F, Hattori S: In situ evaluation of podocin in normal and glomerular diseases. Kidney Int 2003, 64:2092-2099.
  • [11]Mao J, Zhang Y, Du L, Dai Y, Yang C, Liang L: Expression profile of nephrin, podocin, and CD2AP in Chinese children with MCNS and IgA nephropathy. Pediatr Nephrol 2006, 16:1666-1675.
  • [12]Guan N, Ding J, Zhang J, Yang J: Expression of nephrin, podocin, alpha-actinin, and WT1 in children with nephrotic syndrome. Pediatr Nephrol 2003, 18:1122-1127.
  • [13]Machuca E, Benoit G, Nevo F, Tête M-J, Gribouval O, Pawtowski A, Brandström P, Loirat C, Niaudet P, Gubler M-C: Genotype-Phenotype Correlations in Non-Finnish Congenital Nephrotic Syndrome. J Am Soc Nephrol 2010, 21:1209-1217.
  • [14]Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler M-C, Niaudet P, Antignac C: NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000, 24:349-354.
  • [15]Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf E-M, Mucha B: Patients with Mutations in NPHS2 (Podocin) Do Not Respond to Standard Steroid Treatment of Nephrotic Syndrome. J Am Soc Nephrol 2004, 15:722-732.
  • [16]Weber S, Gribouval O, Esquivel EL, Moriniere V, Tete M-J, Legendre C, Niaudet P, Antignac C: NPSH2 mutation analysis show genetic heterogeneity of steroid resistant nephrotic syndrome and low post transplant recurrence. Kidney Int 2004, 66:571-579.
  • [17]He N, Zahirieh A, Mei Y, Lee B, Senthilnathan S, Wong B, Mucha B, Hildebrandt F, Cole DE, Cattran D: Recessive NPHS2 (Podocin) mutations are rare in adult-onset idiopathic focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2007, 2:31-37.
  • [18]Caridi G, Bertelli R, Scolari F, Sanna- Cherchi S, Di Duca M, Ghiggeri GM: Podocin mutations in sporadic focal segmental glomerulosclerosis occurring in adulthood. Kidney Int 2003, 64:365.
  • [19]Tsukaguchi H, Sudhakar A, Le TC, Nguyen T, Yao J, Schwimmer JA, Schachter AD, Poch E, Abreu PF, Appel GB: NPHS2 mutations in late onset focal segmental glomerulosclerosis; R229Q is a common disease associated allele. J Clin Invest 2002, 110:1659-1666.
  • [20]Huber TB, Reinhardt C, Simons M, Petraschka D: Direct binding of cholesterol and targeting to nephrin to lipid rafts are disrupted in disease causing podocin mutation. J Am Soc Nephrol 2004, 15:33A.
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