Lymphatic disruption drives lung transplant fibrosis through interleukin-1-mediated hyaluronan accumulation - PubMed
4 hours ago
- #organ-transplantation
- #lymphatic-disruption
- #fibrosis
- Lymphatic disruption during organ transplantation leads to chronic rejection and fibrosis.
- Fibrosis in transplanted human and mouse lungs and hearts is associated with dysmorphic lymphatics and hyaluronan accumulation.
- A subset of stromal cells in fibrotic grafts coexpress hyaluronan synthase 1 and interleukin-1 receptor 1.
- Interleukin-1β (Il1b) from neutrophils drives hyaluronan synthase 1 up-regulation post-reperfusion.
- Interleukin-1-mediated hyaluronan accumulation causes fibrosis independently of alloimmunity in lymphatic disruption.
- Fibrosis in transplanted mouse lungs can be inhibited by preventing hyaluronan synthesis, accelerating lymphangiogenesis, or blocking interleukin-1 receptor 1 signaling.
- Potential therapeutic strategies include 4-methylumbilliferone, VEGF receptor-3 activation, and interleukin-1 receptor 1 inhibition.