Transforming growth factor-beta and the glomerular extracellular matrix in renal pathology

Transforming growth factor-beta (TGF-beta) is a multifunctionally acting peptide with a broad spectrum of cellular targets. The biologic function of this peptide is currently widely studied. These studies reveal remarkable effects on proliferation, differentiation, migration, and production of many cell types. Among these effects, the regulatory function of TGF-beta in extracellular matrix homeostasis is thought to represent a major part of its action, mediating various other effects. Because disturbance of the regulation of extracellular matrix production is involved in various diseases, TGF-beta was expected to play a role in pathologic accumulation of extracellular matrix. By now, involvement of TGF-beta in the development of pathologic matrix production is most clear in experimental glomerular diseases. In this review, various lines of evidence for such an involvement are presented. After a general introduction about the molecular structure of TGF-beta and its biologic function, the regulation of extracellular matrix production by TGF-beta is discussed, with special emphasis on the glomerulus. Finally, the involvement of TGF-beta in the development of glomerulosclerosis is considered. Because in vivo inhibition of TGF-beta action in animal models seems to prevent pathologic matrix accumulation, the possible role of TGF-beta as an important mediator in the development of glomerulosclerosis may have important implications for prevention of glomerulosclerosis in human renal disease. Extensive study of the in vivo regulation of TGF-beta activity, both in animal models and human diseases, will be necessary for further elucidation of pathogenetic mechanisms and possibilities for therapeutic intervention.