Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis.
OBJECTIVE
There is an intense interest in the potential of circulating blood cells and epithelium-related nonfibroblast cells to change into matrix synthesizing fibroblasts and myofibroblasts. These sources of fibroblasts may have importance in systemic sclerosis (scleroderma).


RESULTS
Epithelial cells from different sources can transition into fibroblasts and myofibroblasts in response to transforming growth factor beta and other growth factors/cytokines. This is called epithelial-mesenchymal transition (EMT). EMT has been repeatedly demonstrated to occur in several models of renal fibrosis including lupus prone mice. Quite unexpectedly, bone morphogenic protein 7 prevents EMT and protects lupus mice and other renal fibrosis models from developing fibrosis in the kidneys. Human peripheral blood mononuclear cells under different conditions of culture give rise to several different types of fibroblast-like cells. In SSc, it has been observed that the sera have low levels of serum amyloid protein. Serum amyloid protein has been found to inhibit the generation of fibrocytes from CD14 precursors. The implications of these potential sources of fibroblasts and myofibroblasts in systemic sclerosis and related rheumatic diseases are discussed.


CONCLUSIONS
Fibroblasts and myofibroblasts in skin and internal organs of patients with systemic sclerosis and related diseases may possibly arise not only from the resident fibroblast population but from epithelial cells, pericytes, monocytes, and other progenitors from the circulating pool of hematopoietic cells and stem cells. These alternative sources of fibroblasts would best be treated by specifically targeting the transition or transdifferentiation process by which cells change into fibroblasts.
Postlethwaite
Arnold E
AE
Division of Connective Tissue Diseases, University of Tennessee Health Science Center, 956 Court Avenue, Room G326, Memphis, TN 38163, USA. apostlethwai@utmem.edu
Shigemitsu
Hidenobu
H
Kanangat
Siva
S
D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D012595:Scleroderma, Systemic / Q000473:pathology*