Sources of myofibroblasts in kidney fibrosis

TY - JOUR

T1 - Sources of myofibroblasts in kidney fibrosis

T2 - all answers are correct, however to different extent!

AU - Ballhause, Tobias M

AU - Soldati, Rocío

AU - Mertens, Peter R

PY - 2014/3

Y1 - 2014/3

N2 - Most inflammatory kidney diseases have the final outcome of fibrosis with the loss of kidney architecture and progressive loss of kidney function. Excess matrix deposition is observed, which may be an inadequate attempt to limit organ damage. The primary sources of matrix synthesis are resident cells that may acquire different activated phenotypes and likely orchestrate matrix deposition. Over the last decades, intense efforts were undertaken to define the origin of myofibroblasts, resulting in four different controversially discussed hypotheses: bone marrow recruitment, vascular pericyte-derived myofibroblasts, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT). In a recent article, LeBleu et al. (Nat Med 19(8):1047-1053, 2013) address this issue and come to the conclusion that most of the different hypotheses are likely true, however to different extents. To arrive at this conclusion, the authors have performed genetic cell tracking and quantification by cell labeling in newly generated knockout mouse models. Quantitative analyses have been made and yield the following estimates: 50% of the myofibroblasts are derived through proliferation from resident fibroblasts, 35% differentiate from bone marrow-derived cells, 10% arise from EndMT, and 5% through EMT.

AB - Most inflammatory kidney diseases have the final outcome of fibrosis with the loss of kidney architecture and progressive loss of kidney function. Excess matrix deposition is observed, which may be an inadequate attempt to limit organ damage. The primary sources of matrix synthesis are resident cells that may acquire different activated phenotypes and likely orchestrate matrix deposition. Over the last decades, intense efforts were undertaken to define the origin of myofibroblasts, resulting in four different controversially discussed hypotheses: bone marrow recruitment, vascular pericyte-derived myofibroblasts, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT). In a recent article, LeBleu et al. (Nat Med 19(8):1047-1053, 2013) address this issue and come to the conclusion that most of the different hypotheses are likely true, however to different extents. To arrive at this conclusion, the authors have performed genetic cell tracking and quantification by cell labeling in newly generated knockout mouse models. Quantitative analyses have been made and yield the following estimates: 50% of the myofibroblasts are derived through proliferation from resident fibroblasts, 35% differentiate from bone marrow-derived cells, 10% arise from EndMT, and 5% through EMT.

KW - Animals

KW - Fibrosis

KW - Humans

KW - Kidney/pathology

KW - Myofibroblasts/cytology

U2 - 10.1007/s11255-013-0626-5

DO - 10.1007/s11255-013-0626-5

M3 - SCORING: Journal article

C2 - 24368748

VL - 46

SP - 659

EP - 664

JO - INT UROL NEPHROL

JF - INT UROL NEPHROL

SN - 0301-1623

IS - 3

ER -