Pathogenesis of diabetic nephropathy: focus on transforming growth factor-beta and connective tissue growth factor. 2001

O V Sakharova, and M W Taal, and B M Brenner
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. osakharova@srhs.org

Although considerable improvement in the prognosis of diabetic nephropathy has been achieved in recent years due to intensive insulin and angiotensin-converting enzyme inhibitor treatment, these approaches do not provide complete protection against progression of diabetic nephropathy. An urgent need for additional novel therapies to prevent or further slow the progression of diabetic nephropathy motivated us to provide an up-to-date review with particular emphasis on the potential role of two growth factors--transforming growth factor-beta and connective tissue growth factor--in the pathogenesis of diabetic nephropathy. The most intensively studied to date, transforming growth factor-beta appears to play a central role in the pathogenesis of diabetic nephropathy. Recently, attention has focused on connective tissue growth factor, which mimics the biological activity of transforming growth factor-beta in profibrotic tissue formation. Thus, acting as a downstream mediator of the profibrotic activity of transforming growth factor-beta, connective tissue growth factor may constitute a more specific target for future antifibrotic therapies.

UI MeSH Term Description Entries
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D003928 Diabetic Nephropathies KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE. Diabetic Glomerulosclerosis,Glomerulosclerosis, Diabetic,Diabetic Kidney Disease,Diabetic Nephropathy,Intracapillary Glomerulosclerosis,Kimmelstiel-Wilson Disease,Kimmelstiel-Wilson Syndrome,Nodular Glomerulosclerosis,Diabetic Kidney Diseases,Glomerulosclerosis, Nodular,Kidney Disease, Diabetic,Kidney Diseases, Diabetic,Kimmelstiel Wilson Disease,Kimmelstiel Wilson Syndrome,Nephropathies, Diabetic,Nephropathy, Diabetic,Syndrome, Kimmelstiel-Wilson
D006133 Growth Substances Signal molecules that are involved in the control of cell growth and differentiation. Mitogens, Endogenous,Endogenous Mitogens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016212 Transforming Growth Factor beta A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk
D055513 Connective Tissue Growth Factor A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It is found in hypertrophic CHONDROCYTES where it may play a role in CHONDROGENESIS and endochondral ossification. CCN2 Protein,Hypertrophic Chondrocyte-Specific Protein 24,IGF-Binding Protein-Related Protein-2,IGFBP-8,IGFBP-rP2,Insulin-Like Growth Factor Binding Protein 8,Hypertrophic Chondrocyte Specific Protein 24,IGF Binding Protein Related Protein 2,Insulin Like Growth Factor Binding Protein 8
D017874 Immediate-Early Proteins Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals. Proteins, Immediate-Early,Immediate Early Proteins,Proteins, Immediate Early
D036341 Intercellular Signaling Peptides and Proteins Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal. Growth Factor,Growth Factors,Paracrine Peptide Factors,Paracrine Protein Factors,Factor, Growth,Factors, Growth,Peptide Factors, Paracrine

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