The findings, reported in this week's Proceedings of the National Academy of Sciences (PNAS), come from collaborative research led by Cincinnati Children's Hospital Medical Center and the Brigham & Women's Hospital of Harvard Medical School.
The study may have significant medical ramifications as currently there are no effective treatments for acute kidney injury – a growing problem in hospitals and clinics, according to the study's senior co-authors, Richard Lang, Ph.D., a researcher in the divisions of Pediatric Ophthalmology and Developmental Biology at Cincinnati Children's, and Jeremy Duffield, M.D., Ph.D., a researcher at Brigham and Women's Hospital. Acute kidney injury is a significant cause of kidney disease, cardiovascular complications and early death, affecting as many as 16 million children and adults in the United States.
The new molecular repair pathway involves white blood cells called macrophages – part of the immune system – that respond to tissue injury by producing a protein called Wnt7b. Scientists identified the macrophage-Wnt7b pathway during experiments in mice with induced kidney injury. Wnt7b is already known to be important to the formation of kidney tissues during embryonic organ development. In this study the scientists found the protein helped initiate tissue repair and regeneration in injured kidneys.
"Our findings suggest that by migrating to the injured kidney and producing Wnt7b, macrophages are re-establishing an early molecular program for organ development that also is beneficial to tissue repair," said Dr. Lang. "This study also indicates the pathway may be important to tissue regeneration and repair in other organs."
Wnt7b is part of the Wnt family of proteins, which are known to help regulate cells as they proliferate, grow and become specific cell types for the body. Wnt proteins have also been linked to the regulation of stem cells in bone marrow and skin, which suggested to researchers of the current study that Wnt might have a role in tissue regeneration.
The researchers conducted a number of experiments of kidney injury in mice to identify the repair pathway, finding that:
Silencing macrophage white blood cells through a process called ablation reduced the response level of Wnt proteins to injured kidney cells.
Deleting the Wnt7b protein from macrophages diminished normal tissue repair functions in injured kidneys.
Injecting into the injured kidneys a protein calked Dkk2, which interacts with and is known to help regulate the Wnt pathway during embryonic development, enhanced the macrophage-Wnt7b repair process. It also restored epithelial surface cells that line internal kidney surfaces and suggested a therapeutic potential for the pathway.
Drs. Lang and Duffield said the repair pathway may benefit other injured organs because macrophages act somewhat like a universal emergency responder in the body, rushing to injured tissues wherever damage occurs. Another factor is the central role the Wnt pathway plays in cell regulation and function throughout the body.
Other collaborating institutions in the study include: the Department of Structural Biology , St, Jude Children's Hospital, Memphis, Tenn.; the departments of Internal Medicine and Molecular Biology, University of Texas Southwest Medical Center; Department of Molecular and Developmental Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, N.Y.; Department of Molecular and Cellular Biology, Harvard University; the Visual Systems Group in the division of Pediatric Ophthalmology at Cincinnati Children's; and the Department of Ophthalmology, University of Cincinnati.
Funding support came from the National Institutes of Health, the American Society of Nephrology Gottschalk Award, the Genzyme Renal Initiatives Program, a National Taiwan Merit Award, and the Abrahamson Pediatric Eye Institute Endowment at Cincinnati Children's.
Nick Miller | EurekAlert!
New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego
Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
17.01.2018 | Ecology, The Environment and Conservation
17.01.2018 | Physics and Astronomy
17.01.2018 | Awards Funding