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Updated: May 29, 2025
Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation
Jie Xu1, Junyan Pu2,3, Hao Chen2,3
1Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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.
Insights
Microvascular pericyte dysfunction significantly worsens outcomes in kidney transplant recipients with antibody-mediated rejection (ABMR). Impaired autophagy is a key mechanism driving this dysfunction and pericyte damage.
Area of Science:
- Nephrology
- Transplantation Immunology
- Cell Biology
Background:
- Antibody-mediated rejection (ABMR) is a major cause of kidney transplant failure.
- The role of microvascular pericyte dysfunction in ABMR pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the contribution of microvascular pericyte dysfunction to antibody-mediated rejection (ABMR) in kidney transplantation.
- To elucidate the underlying mechanisms of pericyte dysfunction in ABMR.
Main Methods:
- Retrospective analysis of 160 kidney transplant patients (ABMR, TCMR, mixed rejection, control groups).
- Immunohistochemistry and immunofluorescence staining for pericyte marker PDGFR-β in graft tissues and mouse models.
- In vitro co-culture models of pericyte and endothelial cells, assessed via Western blotting, PCR, and wound healing assays.
- Bioinformatic analysis (KEGG pathway) of gene expression and electron microscopy for mechanistic insights.
Main Results:
- ABMR patients exhibited significantly poorer renal function indicators (creatinine, urea nitrogen, urine protein, eGFR) compared to other groups.
- Reduced pericyte expression (PDGFR-β) was observed in ABMR kidney grafts and mouse models.
- In vitro studies revealed that pericyte dysfunction impairs vascular endothelial cells, with impaired autophagy identified as a key mechanism.
Conclusions:
- Antibody-mediated rejection (ABMR) episodes negatively impact long-term kidney transplant prognosis.
- Microvascular pericyte dysfunction is a critical factor contributing to poor outcomes in ABMR.
- Impaired autophagy is a significant mechanism underlying microvascular pericyte dysfunction in ABMR, potentially reversible with interventions like chloroquine.
