P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome
Background: P-glycoprotein (P-gp) overexpression in peripheral blood mononuclear cells (PBMCs) has been reported in patients with steroid-resistant nephrotic syndrome (SRNS). Glucocorticoids suppress NFκB-associated coactivator activity by deacetylation of histone by enzyme histone deacetylase (HDAC...
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| Format: | Article |
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2020-01-01
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| Series: | Indian Journal of Rheumatology |
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| Online Access: | http://www.indianjrheumatol.com/article.asp?issn=0973-3698;year=2020;volume=15;issue=1;spage=5;epage=10;aulast=Singh |
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| author | Harshit Singh Narayan Prasad Durga Prasanna Misra Akhilesh Kumar Jaiswal Vikas Agarwal |
| author_facet | Harshit Singh Narayan Prasad Durga Prasanna Misra Akhilesh Kumar Jaiswal Vikas Agarwal |
| author_sort | Harshit Singh |
| collection | DOAJ |
| description | Background: P-glycoprotein (P-gp) overexpression in peripheral blood mononuclear cells (PBMCs) has been reported in patients with steroid-resistant nephrotic syndrome (SRNS). Glucocorticoids suppress NFκB-associated coactivator activity by deacetylation of histone by enzyme histone deacetylase (HDAC)-2. Interaction between HDAC2 activity and P-gp expression in childhood NS patients is not clear.
Aim: This study aims to evaluate the role of HDAC2 and P-gp expression on PBMCs and steroid responsiveness in patients with childhood NS.
Materials and Methods: Thirty-one patients were recruited at baseline (n = 31) (before initiating steroid therapy); after 6 weeks of steroid therapy, 24 patients achieved remission (steroid-sensitive NS [SSNS] n = 24 mean age, 7.96 ± 3.90), whereas seven patients were resistant to steroids (SRNS, n = 7, mean age 10.00 ± 3.55). mRNA expression of HDAC2 and P-gp and functional analysis of P-gp and enzymatic activity of HDAC2 were analyzed at baseline, and at 6 weeks of steroid treatment and at the time of relapse.
Results: The expression of P-gp mRNA was significantly lower in individuals (n = 24) who achieved remission at 6-week steroid therapy as compared to baseline and those who were resistant (n = 7) to steroids (P < 0.005). Similarly, the expression of HDAC2 mRNA was significantly higher at baseline and at remission following 6-week steroid therapy as compared to their expression in those who were resistant to steroids (P < 0.005). The function of P-gp was significantly lower in NS patients who achieved remission after 6-week steroid therapy compared to baseline (P < 0.005), whereas it was not significant in resistant patients (P = 0.37). The enzymatic activity of HDAC2 was significantly higher in SSNS patients as compared SRNS patients at 6-week steroid therapy (P < 0.005).
Conclusion: The expression and function of P-gp and HDAC2 may affect steroid response in NS patients. Combined therapy of steroids with P-gp inhibitor and/or HDAC2 inducers may have a rationale in management of SRNS patients. |
| format | Article |
| id | doaj-art-32b5cc27963a4b67b02ed8a4149d2a1e |
| institution | Kabale University |
| issn | 0973-3698 0973-3701 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Indian Journal of Rheumatology |
| spelling | doaj-art-32b5cc27963a4b67b02ed8a4149d2a1e2025-02-03T00:25:14ZengSAGE PublishingIndian Journal of Rheumatology0973-36980973-37012020-01-0115151010.4103/injr.injr_126_19P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic SyndromeHarshit SinghNarayan PrasadDurga Prasanna MisraAkhilesh Kumar JaiswalVikas AgarwalBackground: P-glycoprotein (P-gp) overexpression in peripheral blood mononuclear cells (PBMCs) has been reported in patients with steroid-resistant nephrotic syndrome (SRNS). Glucocorticoids suppress NFκB-associated coactivator activity by deacetylation of histone by enzyme histone deacetylase (HDAC)-2. Interaction between HDAC2 activity and P-gp expression in childhood NS patients is not clear. Aim: This study aims to evaluate the role of HDAC2 and P-gp expression on PBMCs and steroid responsiveness in patients with childhood NS. Materials and Methods: Thirty-one patients were recruited at baseline (n = 31) (before initiating steroid therapy); after 6 weeks of steroid therapy, 24 patients achieved remission (steroid-sensitive NS [SSNS] n = 24 mean age, 7.96 ± 3.90), whereas seven patients were resistant to steroids (SRNS, n = 7, mean age 10.00 ± 3.55). mRNA expression of HDAC2 and P-gp and functional analysis of P-gp and enzymatic activity of HDAC2 were analyzed at baseline, and at 6 weeks of steroid treatment and at the time of relapse. Results: The expression of P-gp mRNA was significantly lower in individuals (n = 24) who achieved remission at 6-week steroid therapy as compared to baseline and those who were resistant (n = 7) to steroids (P < 0.005). Similarly, the expression of HDAC2 mRNA was significantly higher at baseline and at remission following 6-week steroid therapy as compared to their expression in those who were resistant to steroids (P < 0.005). The function of P-gp was significantly lower in NS patients who achieved remission after 6-week steroid therapy compared to baseline (P < 0.005), whereas it was not significant in resistant patients (P = 0.37). The enzymatic activity of HDAC2 was significantly higher in SSNS patients as compared SRNS patients at 6-week steroid therapy (P < 0.005). Conclusion: The expression and function of P-gp and HDAC2 may affect steroid response in NS patients. Combined therapy of steroids with P-gp inhibitor and/or HDAC2 inducers may have a rationale in management of SRNS patients.http://www.indianjrheumatol.com/article.asp?issn=0973-3698;year=2020;volume=15;issue=1;spage=5;epage=10;aulast=Singhhistone deacetylases 2nephrotic syndromep-glycoproteinsteroid-resistant |
| spellingShingle | Harshit Singh Narayan Prasad Durga Prasanna Misra Akhilesh Kumar Jaiswal Vikas Agarwal P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome Indian Journal of Rheumatology histone deacetylases 2 nephrotic syndrome p-glycoprotein steroid-resistant |
| title | P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome |
| title_full | P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome |
| title_fullStr | P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome |
| title_full_unstemmed | P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome |
| title_short | P-glycoprotein and/or Histone Deacetylase 2 Regulates Steroid Responsiveness in Childhood Nephrotic Syndrome |
| title_sort | p glycoprotein and or histone deacetylase 2 regulates steroid responsiveness in childhood nephrotic syndrome |
| topic | histone deacetylases 2 nephrotic syndrome p-glycoprotein steroid-resistant |
| url | http://www.indianjrheumatol.com/article.asp?issn=0973-3698;year=2020;volume=15;issue=1;spage=5;epage=10;aulast=Singh |
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