TY - JOUR
T1 - Transforming growth factor-Β and kidney dysfunction
AU - Cheng, Jingfei
AU - Grande, Joseph P.
N1 - Funding Information:
This work is supported by a National Institutes of Diabetes and Digestive and Kidney Diseases Grant No. R01 DK16105. We thank Ms. Cherish Grabau for excellent secretarial assistance.
PY - 2009
Y1 - 2009
N2 - In addition to their critical role in embryogenesis of the kidney, members of the transforming growth factor (TGF)-Β superfamily direct a number of pathways important in the maintenance of homeostasis in the differentiated kidney. TGF-Β family members also play an important role in cell-cycle regulation. Through induction of cyclin-dependent kinase inhibitors, TGF-Β promotes a hypertrophic response of renal tubular epithelial cells and glomerular mesangial cells. This TGF-Β driven hypertrophic response, which occurs in diabetic nephropathy, may have deleterious effects on the kidney. In contrast, many human cancers are associated with loss of the growth inhibitory effects of TGF-Β. TGF-Β may promote or inhibit inflammation, an outcome which appears to depend on the cell type(s) involved and on potential interactions with other signaling pathways that regulate inflammatory responses. In recent studies, TGF-Β has been implicated as a key mediator of the epithelial to mesenchymal transition, a process through which epithelial cells acquire characteristics of myofibroblasts which synthesize and deposit extracellular matrix macromolecules and lead to the development of fibrosis, a characteristic feature of chronic renal disease irrespective of etiology. In this brief overview, we highlight recent advances in our understanding of TGF-Β signaling that contribute to the development and progression of chronic renal disease.
AB - In addition to their critical role in embryogenesis of the kidney, members of the transforming growth factor (TGF)-Β superfamily direct a number of pathways important in the maintenance of homeostasis in the differentiated kidney. TGF-Β family members also play an important role in cell-cycle regulation. Through induction of cyclin-dependent kinase inhibitors, TGF-Β promotes a hypertrophic response of renal tubular epithelial cells and glomerular mesangial cells. This TGF-Β driven hypertrophic response, which occurs in diabetic nephropathy, may have deleterious effects on the kidney. In contrast, many human cancers are associated with loss of the growth inhibitory effects of TGF-Β. TGF-Β may promote or inhibit inflammation, an outcome which appears to depend on the cell type(s) involved and on potential interactions with other signaling pathways that regulate inflammatory responses. In recent studies, TGF-Β has been implicated as a key mediator of the epithelial to mesenchymal transition, a process through which epithelial cells acquire characteristics of myofibroblasts which synthesize and deposit extracellular matrix macromolecules and lead to the development of fibrosis, a characteristic feature of chronic renal disease irrespective of etiology. In this brief overview, we highlight recent advances in our understanding of TGF-Β signaling that contribute to the development and progression of chronic renal disease.
KW - Cell cycle
KW - Epithelial to mesenchymal transition
KW - Extracellular matrix accumulation
KW - Progressive renal disease
KW - Signaling, transforming growth factor-Β
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U2 - 10.1080/17471060701649962
DO - 10.1080/17471060701649962
M3 - Review article
AN - SCOPUS:70849105331
SN - 1747-1060
VL - 5
SP - 182
EP - 192
JO - Journal of Organ Dysfunction
JF - Journal of Organ Dysfunction
IS - 3
ER -