PSMP Is Discriminative for Chronic Active Antibody-Mediated Rejection and Associate With Intimal Arteritis in Kidney Transplantation

Abstract

Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which is a key problem associated with the long-term kidney grafts survival. This study investigated the role played by PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR. We showed that CAAMR and CAMR patients’ allografts dysfunction with declined survival rate, which suggested that earlier diagnosis and treatment of CAAMR might be important to prevent irreversible chronic injury of CAMR progression. We found PSMP was an important factor in the development of chronic antibody-mediated rejection. The PSMP expression increased significantly in CAAMR biopsy samples but not in CAMR and control patients, which distinguished CAAMR patients from CAMR and non-rejection patients. Moreover, our results showed that infiltration of CD68+ macrophages in CAAMR increased, and the correlation between CD68+ macrophages and PSMP expression in CAAMR patients was significant. Additionally, our data also revealed that intimal arteritis (v-lesion) accompanied by increased macrophage infiltration might have contributed to more graft loss in CAAMR, and PSMP expression was significantly associated with the v-lesion score. These results indicated that PSMP played an important role in the recruitment of macrophages and promote intimal arteritis inducing allograft lost in CAAMR progression. In future study PSMP could be a potential histopathological diagnostic biomarker and treatment target for CAAMR in kidney transplantation.

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

“…Another study found that PSMP secreted by ovarian cancer cells induced by hypoxia could promote angiogenesis through the MAPK signaling pathway (128). In addition, the expression level of PSMP in patients with chronic active antibody-mediated rejection (CAAMR) has been enormously increased, and there is a significant correlation with the number of infiltrating CD68 + macrophages (129). We found that IL-1b, damage-associated molecule pattern (DAMP) molecules IL-33 and HMGB-1 could induce mouse primary hepatocytes to produce PSMP (32).…”

Transcriptionally Distinct B Cells Infiltrate Allografts After Kidney Transplantation

“…2,3 In particular, mechanisms controlling antibody-mediated rejection (AMR) are poorly understood, resulting in a paucity of specific therapeutic treatments. 4,5 Most inflammatory and regulatory adaptive immune responses after transplantation have been thought to be generated in secondary lymphoid organs. However, newer paradigms suggest that proinflammatory and regulatory alloimmune responses can also be generated and regulated locally within the graft.…”

Global Proteomics Analysis of Lysophosphatidic Acid Signaling in PC-3 Human Prostate Cancer Cells: Role of CCN1

“…Our results show that CCN1 knockdown increased levels of MSMP. The functions of MSMP have not been fully elucidated although it can act as a chemoattractant for macrophages [38]; the latter study indicated that MSMP is a chemokine ligand for the receptor CCR2. MSMP is up-regulated in prostate cancer cells in hypoxic conditions, resulting in increased drug resistance [39].…”