Transformation of interstitial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathy

Abstract

The developmental mechanism of tubulointerstitial fibrosis in diabetic nephropathy (DN) has not been elucidated. Tubulointerstitial fibrosis, as well as glomerulosclerosis, occurs in DN. Myofibroblasts which overproduce extracellular matrix are present in the renal interstitium in diabetics, although they are almost never seen in normal kidneys. The myofibroblasts appear to originate from interstitial fibroblasts. In addition, transforming growth factor-beta1 (TGF-beta 1), which can evoke myofibroblast transformation, is detected in interstitial cells in the diabetic kidney, but not in the normal kidney. Taken together, these findings led us to speculate that TGF-beta 1 induces the transformation of interstitial fibroblasts into myofibroblasts, followed by tubulointerstitial fibrosis. Based on this speculation, we discuss the developmental mechanism of tubulointerstitial fibrosis in this review.

Impact of type 1 diabetes on cardiac fibroblast activation: enhanced cell cycle progression and reduced myofibroblast content in diabetic myocardium

“…Since other studies reported increased myofibroblasts in the kidneys and increased circulating myofibroblast progenitor cells in diabetic patients (13,20,24), we originally hypothesized that diabetic hearts would contain increased myofibroblast content, which would account for the development of cardiac fibrosis. To our surprise, the diabetic myocardium contained significantly less ␣-SMA, indicating fewer myofibroblasts in the diabetic heart.…”

“…High glucose has been shown to stimulate cardiac fibroblast and myofibroblast proliferation in vitro (3,19). Previous studies in other tissues have demonstrated an increase in the myofibroblast population in the kidneys of diabetic rats (13,24). Nguyen et al (20) measured increased myofibroblast progenitor cells in the blood of type 1 diabetic patients.…”

Renal Fibroblasts and Myofibroblasts in Chronic Kidney Disease

“…In the setting of renal fibrosis, myofibroblasts are considered to represent an activated fibroblast phenotype, which is mainly responsible for ECM deposition in tubulointerstitial fibrosis (11). Myofibroblasts are large cells with long processes resembling fibroblasts and VSMC (12). In addition, they are characterized by bundled microfilaments, a welldeveloped rough endoplasmatic reticulum, hemidesmosomes, and other intercellular attachments (11).…”

Effect of Nitric Oxide-cGMP-Dependent Protein Kinase Activation on Advanced Glycation End-Product–Induced Proliferation in Renal Fibroblasts

“…iabetic nephropathy (DN) is characterized by an early period of renal growth with glomerular and tubular cell hypertrophy, but this is followed by progressive glomerulosclerosis and tubulointerstitial fibrosis (1,2). Accumulating studies emphasized the crucial role of renal interstitial fibrosis as a mediator of development of DN (3)(4)(5).…”