Blocking TGF-β1 Protects the Peritoneal Membrane from Dialysate-Induced Damage

Abstract

During peritoneal dialysis (PD), mesothelial cells undergo mesothelial-to-mesenchymal transition (MMT), a process associated with peritoneal-membrane dysfunction. Because TGF-␤1 can induce MMT, we evaluated the efficacy of TGF-␤1-blocking peptides in modulating MMT and ameliorating peritoneal damage in a mouse model of PD. Exposure of the peritoneum to PD fluid induced fibrosis, angiogenesis, functional impairment, and the accumulation of fibroblasts. In addition to expressing fibroblast-specific protein-1 (FSP-1), some fibroblasts co-expressed cytokeratin, indicating their mesothelial origin.

A Pathogenetic Role for Endothelin-1 in Peritoneal Dialysis-Associated Fibrosis

“…[18][19][20][21][22] As such, blocking the action of TGF-b1 by using several strategies has been shown to significantly ameliorate fibrosis and angiogenesis, leading to improved peritoneal function. [23][24][25][26][27] However, because TGF-b1 is physiologically pleiotropic, nondiscriminate targeting of TGF-b1 signaling may result in undesirable side effects. Thus, the identification of potential TGF-b1 downstream targets involved in the action of this cytokine will provide more specific strategies for the preservation of the peritoneal membrane with limited secondary consequences.…”

Specific features of current intraperitoneal therapy in patients with ovarian cancer

“…Хотя фибробласты и не признаны типичными клетка-ми брюшины, однако при нарушениях межклеточных соединений и потере апикально-базолатеральной по-лярности типичные клетки мезотелия превращаются в мигрирующие фибробластоподобные комплексы с повышенными инвазивными и фиброгенными свой-ствами, стимулирующие активный неоангиогенез [10]. Этот процесс, как первая линия обороны против пе-ритонеального карциноматоза, осуществляется за счет TGF-β и может быть активирован применением глю-козы, инфекцией или опухолью [11]. Высокая частота (65 %) асцита у больных РЯ позволяет предположить, что накопление жидкости является активным патоген-ным проявлением болезни и требует прямого воздей-ствия на брюшину лекарственными препаратами (рис.…”

Nano-sized carriers in gene therapy for peritoneal fibrosisin vivo

“…No specific therapy has yet been established for the treatment of peritoneal fibrosis. However, numerous cell types, including mesothelial cells, bone marrow-derived cells, endothelial cells, and fibroblasts, have been reported to contribute to its development [11], and in vivo studies aimed at improving our understanding of the potential therapeutic approaches for peritoneal fibrosis are urgently required. Gene therapy may be a potential therapeutic option because it can target novel molecules that were previously difficult to target using small molecules or antibodies.…”