Vitamin A-coupled liposomes carrying TLR4-silencing shRNA induce apoptosis of pancreatic stellate cells and resolution of pancreatic fibrosis

Abstract

VA-lip-shRNA-TLR4 recovers pancreatic tissue damage. VA-lip-shRNA-TLR4 resolution of pancreatic fibrosis. VA-lip-shRNA-TLR4 accelerates ECM degradation and inhibits ECM synthesis. Silencing TLR4 induces aPSCs mitochondrial apoptosis. Silencing TLR4 inhibits the activation of NF-κB.

Pancreatic Stellate Cells Serve as a Brake Mechanism on Pancreatic Acinar Cell Calcium Signaling Modulated by Methionine Sulfoxide Reductase Expression

“…As mentioned before pancreatic stellate cells all express the cell surface receptor TLR4 [42,43,44,45]. TLR4 agonist LPS was found to induce dose-dependent expression of IL-1, Jak and STAT3 in pancreatic stellate cells, especially of IL-1 (Figure 4A–C).…”

“…Rat pancreatic stellate cells typically express the Toll-like receptor 4, which is activated by TLR4 agonist lipopolysaccharide (LPS) [42,43,44,45]. LPS (0.01, 0.1, 1, 10 mg·L −1 ) stimulation for 24 h was found to increase concentration-dependently the mRNA content of IL-1, Jak, STAT3.…”

“…TLR4 has been found to mediate activation of human pancreatic stellate cells [42]. TLR4 agonist LPS was found to contribute to the development of pancreatic fibrosis, silencing TLR4 expression in pancreatic stellate cells was found to alleviate pancreatic fibrosis [45]. Msr over-expression might therefore overcome these changes that are essential in the development of chronic pancreatitis.…”

Anti-fibrotic treatments for chronic liver diseases: The present and the future

“…Moreover, human and rodent liver myofibroblasts experience constitutive NF-κB activation, which promotes survival by inducing expression of anti-apoptotic genes, such as growth arrest and DNA-damage-inducible 45 beta (Gadd45β) and B-cell lymphoma 2 (Bcl-2) 51 . Therefore, studies on the effectiveness of targeted HSC apoptosis as a therapeutic strategy for liver fibrosis are being actively conducted 52,53 .…”

Role of Retinol Binding Protein in Patients with Pancreatic Diseases

“…Связь между изменением уровня РСБ-4 и раз-витием РПЖ или ХП может быть опосредована через звездчатые клетки стромы поджелудочной железы (ЗКПЖ), которые играют важную роль в патогенезе ХП и РПЖ, при активации регулируя опухолевый рост, метастазирование и влияя на устойчивость опухоли к химиотерапии [38,39]. ЗКПЖ интенсивно накапливают витамин А благодаря активности внутриклеточной фракции РСБ [40]. Активированные ЗКПЖ экспрессируют рецепторы ретиноевой кислоты, которые взаимодействуют с трансретиноевой кислотой -метаболитом витамина А. Активация рецептора витамина А снижает сократительную способность ЗКПЖ и противодействуeт их активации, следовательно, снижается риск развития РПЖ и ХП [39].…”