Ameliorative role of SIRT1 in peritoneal fibrosis: an in vivo and in vitro study

Abstract

Background Peritoneal fibrosis is one of the major complications induced by peritoneal dialysis (PD). Damaged integrity and function of peritoneum caused by peritoneal fibrosis not only limits the curative efficacy of PD and but affects the prognosis of patients. However, the detailed mechanisms underlying the process remain unclear and therapeutic strategy targeting TGF‐β is deficient. Transforming growth factor‐β (TGF‐β) signaling participates in the progression of peritoneal fibrosis through enhancing mesothelial-mesenchymal transition of mesothelial cells. Methods The study aims to demonstrate the regulatory role of Sirtuin1 (SIRT1) to the TGF‐β signaling mediated peritoneal fibrosis. SIRT1−/− mice were used to establish animal model. Masson’s staining and peritoneal equilibration assay were performed to evaluate the degree of peritoneal fibrosis. QRT-PCR assays were used to estimate the RNA levels of Sirt1 and matrix genes related to peritoneal fibrosis, and their protein levels were examined by Western blot assays. Results SIRT1 significantly decreased in vivo post PD treatment. SIRT1 knockout exacerbated peritoneal fibrosis both in vivo and vitro. Overexpression of SIRT1 efficiently inhibited peritoneal fibrosis by inhibiting the peritoneal inflammation and the activation of TGF‐β signaling. Conclusion SIRT1 ameliorated peritoneal fibrosis both in vivo and in vitro through inhibiting the expression of protein matrix induced by TGF‐β signaling.

miR‐128‐3p inhibits high‐glucose‐induced peritoneal mesothelial cells fibrosis via PAK2/SyK/TGF‐β1 axis

“…It makes use of the peritoneal membrane (PM) of human body as a semipermeable membrane to get rid of metabolites and toxic substances in the body and correct the imbalance of water and electrolyte balance via nonstop changes of the dialysate fluid in the abdominal cavity [3,4]. However, the long-term utilization of high-glucose (HG) dialysate may also result in epithelialmesenchymal transformation (EMT) in peritoneal mesothelial cells (PMCs), leading to peritoneal fibrosis (PF) [5,6]. The development of PF is a main challenge for longterm PD [7].…”

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“…SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that is involved in regulating a variety of physiological functions and has been shown to have a therapeutic role in PF [ 80 ]. Guo et al [ 47 ] overexpressed SIRT1 in human umbilical cord-derived MSCs (hUC-MSCs) and demonstrated that SIRT1-modified hUC-MSCs exhibit improved paracrine and posttranscriptional modification abilities that attenuate peritoneal inflammation and fibrosis through the TGF-β/Smad3 pathway.…”

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“…TGF-beta also produces an expansion of the submesothelial extracellular matrix, making the tissue hypoxic; this hypoxia drives a secondary angiogenic response [24]. Consequently, the control of TGF-beta production represents an interesting pharmacological strategy for the prevention of peritoneal fibrosis [25][26][27][28][29].…”