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Our research explores the role of M1 macrophage polarization in endothelium-to-myofibroblast transition (EndMT) and chronic allograft dysfunction (CAD). GSE21374 transcriptome sequencing data were obtained. Transplanted nephrectomy specimens from CAD patients were collected and studied to explore the infiltration of M1 and M2 macrophages using immunofluorescence, PCR, and Western blotting (WB). A co-culture model of M1 macrophages, polarized from mouse bone marrow-derived macrophages (BMDM) or Raw264.7, and aortic endothelial cells was established, and EndMT was tested using PCR and WB. RNA-sequencing was performed on the macrophages from the mouse BMDM. The TNF-α secreted from the polarized M1 macrophages was verified using ELISA. Based on the GEO public database, it was observed that macrophages were significantly infiltrated in CAD allograft tissues, with CD68(+) iNOS(+) M1 macrophages significantly infiltrating the glomeruli of allograft tissues, and CD68(+)CD206(+) M2 macrophages notably infiltrating the allograft interstitial area. The mRNA expression of the M1 macrophage marker inducible nitric oxide synthase (iNOS) was significantly increased (p < 0.05) and M1 macrophages were found to significantly promote the EndMT process in vitro. RNA-Sequencing analysis revealed that TNF signaling could be involved in the EndMT induced by M1 macrophages, and in vitro studies confirmed that TNF-α in the supernatant was significantly higher. The renal allograft tissues of CAD patients were found to be significantly infiltrated by M1 macrophages and could promote the progression of CAD by secreting the cytokine TNF-α to induce EndMT in endothelial cells. [ABSTRACT FROM AUTHOR]

The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD. A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared. MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia. MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation. [ABSTRACT FROM AUTHOR]