Researchers have used a series of genetically engineered mice to identify cellular sources of the
ibrosis that follows kidney injury.
Fibrosis is a common inal pathway for many diseases.
Extensive kidney ibrosis, and the scar tissue that
can sometimes arise from it, can impair the removal
of toxins and excess luid from the blood, cause
irreversible organ damage and, in severe cases, lead to
It is widely accepted that the source of collagen that
causes ibrosis in the kidney is a type of cell called
a myoibroblast. 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 speciic subtypes of cells in the
kidney. The goal was to identify the contribution of
each cell subtype to the process of fibrosis.
The researchers conirmed that myoibroblasts are
a signiicant contributor to kidney ibrosis. They
identiied 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 myoibroblasts but do not proliferate.
(The remaining myoibroblasts were found to be
derived from other sources.) The scientists also found
evidence that pericytes were not a signiicant source of
Understanding the cellular and molecular mediators
of kidney fibrosis is a high priority for scientists
studying kidney disease. This inding is signiicant
because it suggests that treatments for ibrosis that
target myoibroblast proliferation may only be partially
effective, because they have an impact on only about
one-half of the myoibroblast population in the kidney.
A better understanding of ibrosis, 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.
LeBleu VS, Taduri G, O’Connell J, et al. Origin and
function of myoibroblasts in kidney ibrosis. Nat Med 19: