What Accelerate the Renal Fibrosis?

The renal fibrosis referred to the pathological damage process during which a variety of chronic kidney diseases deteriorate into end-stage renal failure. In the process of renal fibrosis, the inflammatory cells infiltrate, and the intrinsic cells have phenotype transformation under the influence of cell factors and growth factors that cause the renal fibrosis. The above cause the form of ECM and the unbalance of degradation, which are the main reason for the renal fibrosis. Renal fibrosis is characterized by the glomerulosclerosis, renal tubular -- interstitial fibrosis, renal vascular fibrosis, and renal vascular sclerosis.
1. Glomerulosclerosis is due to the stimulation from all kinds of pathogenic factors. The stimulation blocks the microcirculation in the glomeruli and causes the ischemia, anoxia. And then, the glomerular capillary endothelial cells are damaged and the endothelial function is out of control.
Under the guidance of MCP-1 chemotactic factor, the activated endothelial cells make the inflammatory cells infiltrate, and produce the IL-1、IL-8、TNF-α、MCP-1、MIP-2, which cause the inflammation. And meanwhile, it damaged the mesangial cell and the glomerular epithelial cells. Then, the mesangial cell proliferate and shrink. The glomerular blood reduce, which makes the glomeruli short of blood and oxygen. After these, the endothelial cells continue to secrete platelet-derived growth factor, (PDGF),and growth factor(TGF-β). With these factors stimulating repeatedly, the mesangial cells
have phenotype transformation, and the epithelial cells proliferate, with foot process running together. As a result, it damages the selective filtration barrier function. The clinical manifestation is protienuria and blood urine.
With PDGF、TGF-β stimulating repeatedly, mesangium cellular phenotype changed into myofibroblast, which secrete and compound collagen Ⅰ、Ⅲ, which is hard to degrade. The collagen Ⅰ、Ⅲ break the dynamic balance and make the ECM gather, so as to replace the intrinsic cells.
renal tubular -- interstitial fibrosis is rooted in glomerular inflammatory cells,( mononuclear- macrophage,T lymphocyte). With the CMP-1leading, it infiltrate to the mesenchyme and release IL-1、IL-2、bFGF, causing inflammatory reaction.
The recurrent inflammation and the proteinuria activate the renal tubular epithelial cells. The activated renal tubular epithelial cells secrete proinflammatory factors (IL-1、CTGF、bFGF、TGF-β、PDGF、MCP-1). The factors in return worsen Interstitial inflammation and make the renal tubular epithelial cells proliferate and grow bigger. What’s worse, renal tubular epithelial cells can also secrete ET-1、AngⅡ.It makes vessels next to the tubules shrink, the renal tubules short of blood, and lead the apoptosis of the epithelial cells. At last, the renal tubules shrink. The stimulation from inflammation and PDGF、TGF-β、EGF、IGF lead the renal tubular epithelial cells to become fibrocytes. EMT come into being.
With the stimulation from Interstitial inflammatory reaction, proinflammatory factors, Promoting fibrosis factors, TFG-β、PDGF, Vascular active factors ET-1, the intrinsic cells in the mesenchyme shows Fiber cell activation, and secrete collagen Ⅰ、Ⅲ、Ⅳ、Ⅴ、FN. Then, the intrinsic cells become fiber cells and proliferate. Now, the fiber cells from the mesenchyme and the fibroblast from renal tubular epithelial cells turn to myofibroblast (MyoF) due to the stimulation from PDGF、TGF-β.Then, the (MyoF)secrete collagen Ⅰ、Ⅲ,which cause the ECM gather.
Meanwhile, the MyoF promote the combination of TIMPs、PAI which restrain the degrading enzymes, inhibit the ECM degradation from MMPs and PA so as to destroy the balance function which can cause and degrade ECM. In the end stage, MyoF will not be influenced by the stimulation from PDGF、TGF-β. It compounds and secretes a large amount of collagen Ⅰ、Ⅲ, which is hard to degrade. This causes the ECM gather abnormally, and then interstitial fibrosis comes into being.
Renal vascular fibrosis and renal vascular sclerosis speed up the renal fibrosis.
The constant high blood pressure in the body causes the expansion of the afferent arterioles. The expand causes the glomeruli are under high pressure and short of oxygen: for another, the constant high blood pressure in the body can also cause the expand of the efferent arterioles. The latter expansion will cause high blood pressure in the vessels next to the kidney tubules, the endothelium of the blood capillary damaged, which form and worsen the fibrosis.
The high blood pressure in the glomeruli stimulate the PDGF、AngⅡ、ET-1 to release. It also stimulates the smooth muscle cells in the different grade of renal arterial wall and the interstitial fibroblasts, and causes them to proliferate.
The shrink of the vessels makes the renal arteriole narrow, and hard. Arteriosclerosis will cause Ischemia hypoxia, and worsen the fibrosis. It causes the apoptosis of the renal tubular epithelial cells and renal tubular atrophy, which speed up the glomerulosclerosis and the interstitial fibrosis.