2013
DOI: 10.1038/nm.3218
|View full text |Cite
|
Sign up to set email alerts
|

Origin and function of myofibroblasts in kidney fibrosis

Abstract: Myofibroblasts are associated with organ fibrosis but their precise origin and functional role remain unknown. We employed multiple genetically engineered mice to track, fate-map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Such comprehensive analysis identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts via proliferation. The non-proliferating myofibroblasts derive via differentiation from bone marrow (35%), e… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

25
1,013
2
7

Year Published

2014
2014
2023
2023

Publication Types

Select...
8
1

Relationship

1
8

Authors

Journals

citations
Cited by 1,090 publications
(1,047 citation statements)
references
References 38 publications
25
1,013
2
7
Order By: Relevance
“…Myofibroblasts are the primary source of extracellular matrix (ECM), which is deposited in the renal interstitium during fibrogenesis. The anatomic origin of interstitial myofibroblasts responsible for excessive matrix production is still an area of controversy, and various origins have been proposed including adult kidney nephrogenic progenitors, stroma, bone marrow-derived cells, damaged epithelium, and endothelium (3,(7)(8)(9)(10)(11)(12)(13)(14)(15). Most likely, interstitial myofibroblasts in renal fibrosis originate from multiple sources but to various extents; the majority, however, appears to originate from the FOXD1 lineage, which gives rise to pericytes, Abbreviations: ATA, acetylthioacetate; DMF, dimethylformamide; ECM, extracellular matrix; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GMBS, g-maleimidobutyryloxy-succinimide ester; HRP, horseradish peroxidase; HSA, human serum albumin; IF, interstitial fibrosis; IFN-gR1, IFN-g receptor 1; JAK/STAT, Janus kinase/signal transducers and activators of transcription signaling pathway; LTA, lotus tetragonolobus; LTL, lotus tetragonolobus lectin;…”
mentioning
confidence: 99%
“…Myofibroblasts are the primary source of extracellular matrix (ECM), which is deposited in the renal interstitium during fibrogenesis. The anatomic origin of interstitial myofibroblasts responsible for excessive matrix production is still an area of controversy, and various origins have been proposed including adult kidney nephrogenic progenitors, stroma, bone marrow-derived cells, damaged epithelium, and endothelium (3,(7)(8)(9)(10)(11)(12)(13)(14)(15). Most likely, interstitial myofibroblasts in renal fibrosis originate from multiple sources but to various extents; the majority, however, appears to originate from the FOXD1 lineage, which gives rise to pericytes, Abbreviations: ATA, acetylthioacetate; DMF, dimethylformamide; ECM, extracellular matrix; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GMBS, g-maleimidobutyryloxy-succinimide ester; HRP, horseradish peroxidase; HSA, human serum albumin; IF, interstitial fibrosis; IFN-gR1, IFN-g receptor 1; JAK/STAT, Janus kinase/signal transducers and activators of transcription signaling pathway; LTA, lotus tetragonolobus; LTL, lotus tetragonolobus lectin;…”
mentioning
confidence: 99%
“…Clearly, all proposed markers had deficiencies, creating an as-yet unresolved dispute in the field regarding identity of fibroblasts and their respective function in kidney health and disease. The confusion is further fueled by assumed different origins of fibroblasts in diseased kidneys (for extensive information, see elsewhere [4,29]). For practical purposes, we here define fibroblasts as the nonvascular, nonepithelial, and noninflammatory cell constituents of the kidney (11).…”
Section: Heterogeneity Of Renal Fibroblastsmentioning
confidence: 99%
“…Other embryonic sources were also proposed, for example from protein zero (P0) neural crest progenitors (166). A considerable number of studies have tackled the source of myofibroblasts during renal fibrosis (22,62,67,83,(172)(173)(174)(175)(176)(177)(178). In short, and in our opinion, the majority, if not all myofibroblasts arise from resident interstitial mesenchymal cells.…”
Section: The Role Of Interstitial Mesenchymal Cellsmentioning
confidence: 99%
“…Both fibrocytes and tubular cells can acquire features of mesenchymal phenotypes (179) and contribute to fibrosis by paracrine effects on neighboring fibroblasts. Another potential source of myofibroblasts are endothelial cells of peritubular capillaries via so-called endothelial-tomesenchymal transition (180,181) but this source is also controversial (65,67,182).…”
Section: The Role Of Interstitial Mesenchymal Cellsmentioning
confidence: 99%