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Tracking the Origins of Kidney Fibrosis

Researchers have used a series of genetically engineered mice to identify cellular sources of the fibrosis that follows kidney injury.

Fibrosis is a common final pathway for many diseases. Extensive kidney fibrosis, and the scar tissue that can sometimes arise from it, can impair the removal of toxins and excess fluid from the blood, cause irreversible organ damage and, in severe cases, lead to kidney failure.

It is widely accepted that the source of collagen that causes fibrosis in the kidney is a type of cell called a myofibroblast. Previous research suggested that these cells might be derived from pericytes, a type of cell associated with blood vessels. In the new study, the scientists developed a number of different strains of mice in which they could visualize, track, and selectively eliminate specific subtypes of cells in the kidney. The goal was to identify the contribution of each cell subtype to the process of fibrosis.

The researchers confirmed that myofibroblasts are a significant contributor to kidney fibrosis. They identified two primary sources for these cells: about half of them result from conversion of existing precursor cells in the kidney, which then proliferate, while about one third arise from precursors produced in the bone marrow that travel to the kidney and convert to myofibroblasts but do not proliferate. (The remaining myofibroblasts were found to be derived from other sources.) The scientists also found evidence that pericytes were not a significant source of myofibroblasts.

Understanding the cellular and molecular mediators of kidney fibrosis is a high priority for scientists studying kidney disease. This finding is significant because it suggests that treatments for fibrosis that target myofibroblast proliferation may only be partially effective, because they have an impact on only about one-half of the myofibroblast population in the kidney. A better understanding of fibrosis, in general, could yield insights into how this process unfolds in other tissues and organs, potentially opening new avenues to therapy for a range of diseases.


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