Bad and good growth factors in the peritoneal cavity (Review Article)

Abstract

SUMMARY: Progressive peritoneal membrane fibrosis, and associated loss of ultrafiltration and dialysis capacity, is an increasingly limiting problem with time on peritoneal dialysis. The primary culprit is the composition of the peritoneal dialysate, although episodes of peritonitis can hasten the process. At a molecular level, there is increasing evidence that several growth factors play key roles in the development of peritoneal membrane fibrosis. Transforming growth factor (TGF)‐β is widely implicated in pathological fibrosis, and a considerable body of evidence favours a similar role in the peritoneal membrane. Connective tissue growth factor (CTGF), a downstream mediator of TGF‐β‐induced fibrosis, has more recently been implicated in peritoneal membrane scarring. In contrast to the pleiotropic effects of TGF‐β, CTGF more specifically targets the fibrosis pathway, and so is an attractive candidate for inhibiting the damage to the membrane. Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) has also been found in the peritoneal cavity, but its effect on peritoneal mesothelial cells suggests that it has a positive role in guiding membrane repair and avoiding pathological fibrosis. In the future, it is hoped that changes in peritoneal dialysis technology will create a better balance between the bad and good effects of these growth factors, which in turn will lead to more successful long‐term outcomes for this major renal replacement therapy.

Aliskiren ameliorates chlorhexidine digluconate‐induced peritoneal fibrosis in rats

“…TGF‐β1 is a profibrotic cytokine that has been shown to regulate PF [10,24]. The overexpression of TGF‐β1 further increases α‐SMA, VEGF and promotes PF through extensive collagen deposition and neoangiogenesis [25].…”

The Role of Tyrosine Kinase Receptors in Peritoneal Fibrosis

“…In contrast, Faull et al argued that HB-EGF is normally present in the peritoneal cavity and is a helpful growth factor at this site, where it facilitates appropriate repair of the mesothelial cell layer and the peritoneal membrane (43). Since loss of mesothelial cells occurs during peritonitis or over time on PD, depletion of this source of HB-EGF may diminish its "beneficial" properties (43).…”

Treatment of Established Peritoneal Fibrosis by Gene Transfer of Smad7 in a Rat Model of Peritoneal Dialysis

“…ment therapy [1][2][3][4] . Thus, it is important to develop new therapeutic strategies by specifically targeting mediators or pathways responsible for peritoneal fibrosis.…”