Researchers discover pathway that helps lead to kidney transplant rejection

Researchers have identified a new pathway that likely plays an important role in rejection following kidney transplantation. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), point to a promising strategy to help protect the health of recipients and the function of transplanted organs.

When a team led by Hui Yao Lan MD, PhD from The Chinese University of Hong Kong, and Jiang Hua Chen, MD, from Zhejiang University, examined biopsy specimens from patients experiencing kidney rejection, the researchers found that certain immune cells were transforming into connective tissue cells, which produce collagen and other fibers.

The extent of this so-called macrophage-to-myofibroblast transition correlated with the severity of fibrosis and with the transplanted kidney’s function.

“In this study, we discovered that inflammatory macrophages are an important cell capable of driving the process from acute kidney inflammation to chronic kidney fibrosis during allograft rejection via a new pathway called the macrophage-to-myofibroblast transition,” said Lan.

The macrophage-to-myofibroblast transition was also apparent in mouse transplant models and was mediated through what’s known as the TGF-/Smad3 signaling pathway.

“These findings suggest that specifically targeting alterative macrophages or the TGF-/Smad3 pathway may help prevent or treat tissue scarring,” said Chen.

Study co-authors include Ying-Ying Wang, MD, PhD; Hong Jiang, PhD; Jun Pan, MD, PhD; Xiao-Ru Huang, MD, PhD; Yu-Cheng Wang, BS; Hong-Feng Huang, MD, Ka-Fei To, MD; and David Nikolic-Paterson, PhD.