- During rejection of a transplanted kidney, certain immune cells transform into connective tissue cells, which produce collagen and other fibers.
- This transition, which is mediated by the TGF-/Smad3 signaling pathway, leads to scarring and decreased kidney function.
Washington, DC (February 16, 2017) -- 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.
Fibrosis, or tissue scarring, is a significant contributor to organ loss after transplantation. Inflammatory immune cells are associated with fibrosis in transplanted kidneys, but how these cells contribute to this damaging response is not clearly understood.
When a team led by Hui Yao Lan MD, PhD (The Chinese University of Hong Kong) and Jiang Hua Chen, MD (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 Dr. 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 Dr. 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.
Disclosures: This study was supported by the Research Grants Council of Hong Kong, the Focused Investment Scheme and CRF matching found from The Chinese University of Hong Kong, the Major State Basic Research Development Program of China, the National Nature Science Foundation of China, and the National Fund Committee of China. Dr. David Nikolic-Paterson is supported by the National Health Medical Research Council of Australia.
The article, entitled "Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury," will appear online at http://jasn.asnjournals.org/ on February 16, 2017, doi: 10.1681/ASN.2016050573.
The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.
Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 17,000 members representing 112 countries. For more information, please visit http://www.asn-online.org or contact the society at 202-640-4660.
Journal of the American Society of Nephrology