Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation

Objective To investigate the role of microvascular pericyte dysfunction in antibody-mediated rejection (ABMR) of transplanted kidneys.Methods A total of 160 patients who underwent kidney transplantation in our hospital from 2004 to 2020 were enrolled, divided into 4 groups: ABMR group (n = 79), TCMR...

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Main Authors: Jie Xu, Junyan Pu, Hao Chen, Li Sun, Shuang Fei, Zhijian Han, Jun Tao, Xiaobing Ju, Zijie Wang, Ruoyun Tan, Min Gu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2458749
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author Jie Xu
Junyan Pu
Hao Chen
Li Sun
Shuang Fei
Zhijian Han
Jun Tao
Xiaobing Ju
Zijie Wang
Ruoyun Tan
Min Gu
author_facet Jie Xu
Junyan Pu
Hao Chen
Li Sun
Shuang Fei
Zhijian Han
Jun Tao
Xiaobing Ju
Zijie Wang
Ruoyun Tan
Min Gu
author_sort Jie Xu
collection DOAJ
description Objective To investigate the role of microvascular pericyte dysfunction in antibody-mediated rejection (ABMR) of transplanted kidneys.Methods A total of 160 patients who underwent kidney transplantation in our hospital from 2004 to 2020 were enrolled, divided into 4 groups: ABMR group (n = 79), TCMR group (n = 20), mixed rejection group (n = 25) and control group (n = 36). Postoperative renal function indicators were compared, and immunohistochemical and immunofluorescence staining was performed on graft tissues and mice models using the pericyte marker PDGFR-β. An in vitro pericyte dysfunction model was co-cultured with vascular endothelial cells for functional assessment through Western blotting, PCR, and wound healing tests. KEGG pathway analysis from the GEO database identified gene expression changes in pericytes, which were further analyzed using electron microscopy and Western blot techniques.Results There were statistically significant differences in creatinine, urea nitrogen, urine protein, and eGFR among the groups over time, with ABMR displaying the poorest outcomes. Immunohistochemistry revealed lower pericyte expression in ABMR, which was confirmed in mouse model studies showing reduced PDGFR-β expression in ABMR. KEGG analysis highlighted decreased autophagy in pericyte dysfunction, supported by electron microscopy and Western blot findings indicating reduced autophagy and pericyte damage, which could be reversed by chloroquine.Conclusion ABMR episodes worsened the long-term prognosis of transplanted kidneys. pericyte dysfunction appears to be one of the crucial causes of poor prognosis in ABMR patients. In vitro studies demonstrated that dysfunction of microvascular pericytes can result in damage to vascular endothelial cells, with autophagy impairment being a significant mechanism contributing to pericyte dysfunction.
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spelling doaj-art-2ba035f8b599426fab3b4b6aa62954392025-02-06T06:37:25ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2458749Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantationJie Xu0Junyan Pu1Hao Chen2Li Sun3Shuang Fei4Zhijian Han5Jun Tao6Xiaobing Ju7Zijie Wang8Ruoyun Tan9Min Gu10Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDeparment of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaObjective To investigate the role of microvascular pericyte dysfunction in antibody-mediated rejection (ABMR) of transplanted kidneys.Methods A total of 160 patients who underwent kidney transplantation in our hospital from 2004 to 2020 were enrolled, divided into 4 groups: ABMR group (n = 79), TCMR group (n = 20), mixed rejection group (n = 25) and control group (n = 36). Postoperative renal function indicators were compared, and immunohistochemical and immunofluorescence staining was performed on graft tissues and mice models using the pericyte marker PDGFR-β. An in vitro pericyte dysfunction model was co-cultured with vascular endothelial cells for functional assessment through Western blotting, PCR, and wound healing tests. KEGG pathway analysis from the GEO database identified gene expression changes in pericytes, which were further analyzed using electron microscopy and Western blot techniques.Results There were statistically significant differences in creatinine, urea nitrogen, urine protein, and eGFR among the groups over time, with ABMR displaying the poorest outcomes. Immunohistochemistry revealed lower pericyte expression in ABMR, which was confirmed in mouse model studies showing reduced PDGFR-β expression in ABMR. KEGG analysis highlighted decreased autophagy in pericyte dysfunction, supported by electron microscopy and Western blot findings indicating reduced autophagy and pericyte damage, which could be reversed by chloroquine.Conclusion ABMR episodes worsened the long-term prognosis of transplanted kidneys. pericyte dysfunction appears to be one of the crucial causes of poor prognosis in ABMR patients. In vitro studies demonstrated that dysfunction of microvascular pericytes can result in damage to vascular endothelial cells, with autophagy impairment being a significant mechanism contributing to pericyte dysfunction.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2458749Microvascular pericyte dysfunctionkidney transplantationantibody-mediated rejectionendothelial cell damagelong-term prognosis
spellingShingle Jie Xu
Junyan Pu
Hao Chen
Li Sun
Shuang Fei
Zhijian Han
Jun Tao
Xiaobing Ju
Zijie Wang
Ruoyun Tan
Min Gu
Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
Renal Failure
Microvascular pericyte dysfunction
kidney transplantation
antibody-mediated rejection
endothelial cell damage
long-term prognosis
title Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
title_full Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
title_fullStr Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
title_full_unstemmed Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
title_short Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
title_sort role of microvascular pericyte dysfunction in antibody mediated rejection following kidney transplantation
topic Microvascular pericyte dysfunction
kidney transplantation
antibody-mediated rejection
endothelial cell damage
long-term prognosis
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2458749
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