Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner.
BACKGROUND
Fibrosis, or scar formation, is a pathological condition characterized by excessive production and accumulation of collagen, loss of tissue architecture, and organ failure in response to uncontrolled wound healing. Several cellular populations have been implicated, including bone marrow-derived circulating fibrocytes, endothelial cells, resident fibroblasts, epithelial cells, and recently, perivascular cells called pericytes. We previously demonstrated pericyte functional heterogeneity in skeletal muscle. Whether pericyte subtypes are present in other tissues and whether a specific pericyte subset contributes to organ fibrosis are unknown.


METHODS
Here, we report the presence of two pericyte subtypes, type-1 (Nestin-GFP-/NG2-DsRed+) and type-2 (Nestin-GFP+/NG2-DsRed+), surrounding blood vessels in lungs, kidneys, heart, spinal cord, and brain. Using Nestin-GFP/NG2-DsRed transgenic mice, we induced pulmonary, renal, cardiac, spinal cord, and cortical injuries to investigate the contributions of pericyte subtypes to fibrous tissue formation in vivo.


RESULTS
A fraction of the lung's collagen-producing cells corresponds to type-1 pericytes and kidney and heart pericytes do not produce collagen in pathological fibrosis. Note that type-1, but not type-2, pericytes increase and accumulate near the fibrotic tissue in all organs analyzed. Surprisingly, after CNS injury, type-1 pericytes differ from scar-forming PDGFRβ + cells.


CONCLUSIONS
Pericyte subpopulations respond differentially to tissue injury, and the production of collagen by type-1 pericytes is organ-dependent. Characterization of the mechanisms underlying scar formation generates cellular targets for future anti-fibrotic therapeutics.
Alexander
A
Birbrair
Tan
T
Zhang
Daniel Clark
DC
Files
Sandeep
S
Mannava
Thomas
T
Smith
Zhong-Min
ZM
Wang
Maria Laura
ML
Messi
Akiva
A
Mintz
Osvaldo
O
Delbono
D000818:Animals; D002921:Cicatrix / Q000473:pathology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D020286:Pericytes / Q000145:classification* / Q000378:metabolism
D064231:Nestin; D003094:Collagen