Dietary carboxymethylcellulose metabolite promotes heart allograft rejection through induction of pro-inflammatory macrophages via lysophosphatidic acid - PubMed
3 days ago
- #Carboxymethylcellulose
- #Heart transplant rejection
- #Macrophage polarization
- Dietary carboxymethylcellulose (CMC) promotes heart allograft rejection by inducing pro-inflammatory macrophages via lysophosphatidic acid (LPA).
- CMC-fed mice showed increased LPA-producing bacteria and higher serum LPA levels, leading to transplant rejection.
- Fecal microbiota transplantation and gut microbiota depletion confirmed the role of gut microbiota in CMC-induced rejection.
- LPA-treated macrophages accelerated allograft rejection by upregulating glycolysis, while glycolysis inhibitors promoted allograft survival.
- Human transplant rejection patients had elevated serum LPA levels and LPAR6 expression in graft-infiltrating macrophages.
- LPA promoted LPAR6 expression, activating the mTOR/HIF-1α pathway to enhance glycolysis and pro-inflammatory macrophage polarization.
- Treatment with LPAR antagonist Ki16425 prolonged allograft survival in CMC-fed recipients.