Thalidomide alleviated IgA nephropathy through “gut-kidney axis”
Objective Thalidomide has anti-inflammatory, immunomodulatory and renoprotective effects. However, its study in IgA nephropathy has remained scarce. The aim was to explore the role and possible mechanism of thalidomide in IgA nephropathy. Methods MicroRNA-23b-3p-/-（miR-23b-/-） mice were selected as...
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Editorial Department of Journal of Clinical Nephrology
2024-12-01
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| Series: | Linchuang shenzangbing zazhi |
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| Online Access: | http://www.lcszb.com/cn/article/doi/10.3969/j.issn.1671-2390.2024.12.007 |
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| author | Rui-hua Wang Zhi-jian Zha Zi-yang Ye Ya-feng Li |
| author_facet | Rui-hua Wang Zhi-jian Zha Zi-yang Ye Ya-feng Li |
| author_sort | Rui-hua Wang |
| collection | DOAJ |
| description | Objective Thalidomide has anti-inflammatory, immunomodulatory and renoprotective effects. However, its study in IgA nephropathy has remained scarce. The aim was to explore the role and possible mechanism of thalidomide in IgA nephropathy. Methods MicroRNA-23b-3p-/-（miR-23b-/-） mice were selected as IgA nephropathy model animal. And four groups of model, high-dose thalidomide, low-dose thalidomide and blank control were set up for 8-week intervention. The changes of renal tissue structure, IgA kidney deposition, urinary microalbumin and ileal histomorphology were recorded. The expression of intestinal barrier protein was detected by immunohistochemistry. And enzyme-linked immunosorbent assay（ELISA） was utilized for detecting the levels of interleukin-18 （IL-18） and interleukin-1β （IL-1β） in murine intestine. Western blot was employed for detecting the levels of NLR family, pyrin domain-containing 3 protein（NLRP3） inflammasome related protein, apoptosis-related speck-like protein containing CARD （ASC） and cysteinyl aspartate specific proteinase 1（caspase 1） levels. Results Both low-dose thalidomide and high-dose thalidomide resulted in a reversal of renal histomorphometric destruction in IgA nephropathic mice. There were declines in 24-hour urinary protein quantification in low-dose thalidomide group [（0.5540±0.2454） mg vs （0.2513±0.1238） mg] and high-dose thalidomide group[（0.5540±0.2454） vs （0.3756±0.0992） mg]（P＜0.05）, low-dose thalidomide group[（41.65±15.9） vs （28.21±3.839） μmol/L], high-dose thalidomide group [（41.65±15.93） vs （15.67±5.695） μmol/L]. Blood creatinine dropped and the difference was statistically significant in high-dose thalidomide group（P＜0.05）. Immunofluorescence revealed a decrease in IgA deposition. In model group, ileal tissue morphology was pathologically altered and immunohistochemical stain showed that the levels of intestinal mechanical barrier proteins occludin, ZO-1 and MUC-2 declined （P＜0.05）. After a treatment of low/high-dose thalidomide, ileal tissue alterations were restored and the levels of intestinal mechanical barriers both rebounded （P＜0.05）. As compared with IgA nephropathy mice in low-dose thalidomide group[IL-18（80.52±13.16） vs （39.98±12.41） ng/L, IL-1β（0.9459±0.2347） vs （0.4048±0.2389） ng/L] and high-dose thalidomide group[IL-18（80.52±13.16） vs （49.90±15.07） ng/L, IL-1β （0.9459±0.2347） vs （0.4336±0.1472） ng/L], murine ileum showed lower levels of IL-18 （P＜0.05） and IL-1β（P＜0.05）. Protein immunoblot indicated that thalidomide arrested the activation of NLRP3, ASC and caspase1 in murine ileum and the differences were statistically significant（P＜0.05）. Conclusion Thalidomide alleviates renal disease in mice with IgA nephropathy through suppressing NLRP3 inflammasome and inducing intestinal inflammation for restoring intestinal barrier. |
| format | Article |
| id | doaj-art-bdba78ee8844457b8c2ec1e0af9759b9 |
| institution | OA Journals |
| issn | 1671-2390 |
| language | zho |
| publishDate | 2024-12-01 |
| publisher | Editorial Department of Journal of Clinical Nephrology |
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| series | Linchuang shenzangbing zazhi |
| spelling | doaj-art-bdba78ee8844457b8c2ec1e0af9759b92025-08-20T02:35:32ZzhoEditorial Department of Journal of Clinical NephrologyLinchuang shenzangbing zazhi1671-23902024-12-0124121017102710.3969/j.issn.1671-2390.2024.12.00720240042Thalidomide alleviated IgA nephropathy through “gut-kidney axis”Rui-hua Wang0Zhi-jian Zha1Zi-yang Ye2Ya-feng Li3College III of Clinical Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, ChinaSchool of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430065, ChinaCollege III of Clinical Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, ChinaCollege III of Clinical Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, ChinaObjective Thalidomide has anti-inflammatory, immunomodulatory and renoprotective effects. However, its study in IgA nephropathy has remained scarce. The aim was to explore the role and possible mechanism of thalidomide in IgA nephropathy. Methods MicroRNA-23b-3p-/-（miR-23b-/-） mice were selected as IgA nephropathy model animal. And four groups of model, high-dose thalidomide, low-dose thalidomide and blank control were set up for 8-week intervention. The changes of renal tissue structure, IgA kidney deposition, urinary microalbumin and ileal histomorphology were recorded. The expression of intestinal barrier protein was detected by immunohistochemistry. And enzyme-linked immunosorbent assay（ELISA） was utilized for detecting the levels of interleukin-18 （IL-18） and interleukin-1β （IL-1β） in murine intestine. Western blot was employed for detecting the levels of NLR family, pyrin domain-containing 3 protein（NLRP3） inflammasome related protein, apoptosis-related speck-like protein containing CARD （ASC） and cysteinyl aspartate specific proteinase 1（caspase 1） levels. Results Both low-dose thalidomide and high-dose thalidomide resulted in a reversal of renal histomorphometric destruction in IgA nephropathic mice. There were declines in 24-hour urinary protein quantification in low-dose thalidomide group [（0.5540±0.2454） mg vs （0.2513±0.1238） mg] and high-dose thalidomide group[（0.5540±0.2454） vs （0.3756±0.0992） mg]（P＜0.05）, low-dose thalidomide group[（41.65±15.9） vs （28.21±3.839） μmol/L], high-dose thalidomide group [（41.65±15.93） vs （15.67±5.695） μmol/L]. Blood creatinine dropped and the difference was statistically significant in high-dose thalidomide group（P＜0.05）. Immunofluorescence revealed a decrease in IgA deposition. In model group, ileal tissue morphology was pathologically altered and immunohistochemical stain showed that the levels of intestinal mechanical barrier proteins occludin, ZO-1 and MUC-2 declined （P＜0.05）. After a treatment of low/high-dose thalidomide, ileal tissue alterations were restored and the levels of intestinal mechanical barriers both rebounded （P＜0.05）. As compared with IgA nephropathy mice in low-dose thalidomide group[IL-18（80.52±13.16） vs （39.98±12.41） ng/L, IL-1β（0.9459±0.2347） vs （0.4048±0.2389） ng/L] and high-dose thalidomide group[IL-18（80.52±13.16） vs （49.90±15.07） ng/L, IL-1β （0.9459±0.2347） vs （0.4336±0.1472） ng/L], murine ileum showed lower levels of IL-18 （P＜0.05） and IL-1β（P＜0.05）. Protein immunoblot indicated that thalidomide arrested the activation of NLRP3, ASC and caspase1 in murine ileum and the differences were statistically significant（P＜0.05）. Conclusion Thalidomide alleviates renal disease in mice with IgA nephropathy through suppressing NLRP3 inflammasome and inducing intestinal inflammation for restoring intestinal barrier.http://www.lcszb.com/cn/article/doi/10.3969/j.issn.1671-2390.2024.12.007glomerulonephritis, igathalidomidegut-kidney axisintestinal barrier functionnucleotide-binding oligomerization domain-like receptorprotein 3-inflammasome |
| spellingShingle | Rui-hua Wang Zhi-jian Zha Zi-yang Ye Ya-feng Li Thalidomide alleviated IgA nephropathy through “gut-kidney axis” Linchuang shenzangbing zazhi glomerulonephritis, iga thalidomide gut-kidney axis intestinal barrier function nucleotide-binding oligomerization domain-like receptorprotein 3-inflammasome |
| title | Thalidomide alleviated IgA nephropathy through “gut-kidney axis” |
| title_full | Thalidomide alleviated IgA nephropathy through “gut-kidney axis” |
| title_fullStr | Thalidomide alleviated IgA nephropathy through “gut-kidney axis” |
| title_full_unstemmed | Thalidomide alleviated IgA nephropathy through “gut-kidney axis” |
| title_short | Thalidomide alleviated IgA nephropathy through “gut-kidney axis” |
| title_sort | thalidomide alleviated iga nephropathy through gut kidney axis |
| topic | glomerulonephritis, iga thalidomide gut-kidney axis intestinal barrier function nucleotide-binding oligomerization domain-like receptorprotein 3-inflammasome |
| url | http://www.lcszb.com/cn/article/doi/10.3969/j.issn.1671-2390.2024.12.007 |
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