RNA-Binding Protein HuR Regulates Paneth Cell Function by Altering Membrane Localization of TLR2 via Post-transcriptional Control of CNPY3

Long Noncoding RNA H19 Impairs the Intestinal Barrier by Suppressing Autophagy and Lowering Paneth and Goblet Cell Function

“…Interestingly, H19 knockout enhanced the functions of Paneth cells (lysozyme-positive cells) and goblet cells (determined by Alcian blue staining in vivo and mucin 2 immunostaining ex vivo) in the small intestinal mucosa. As reported, 7,8 Paneth cells normally were located at the base of the crypt in littermate mice, but the numbers of these lysozyme-positive cells increased significantly in H19 -/mice relative to control littermate mice (Figure 2A and B, top panel). The number of lysozyme-positive cells in the intestinal epithelium from H19-deficient mice increased by approximately 20% compared with those from control littermate mice.…”

“…6 In response to bacterial infection of the intestines, Paneth cells secrete lysozyme through secretory autophagy 7 and their function is tightly regulated at the posttranscriptional level by the RNA binding protein HuR. 8 Autophagy is a conserved intracellular pathway that sequesters cytoplasmic structures and pathogens targeted for degradation. 9,10 Intestinal barrier dysfunction occurs commonly in various pathologies, leading to leaky gut and structural abnormalities of the epithelium.…”

“…45 Defects in Paneth and goblet cells disrupt the intestinal barrier function and compromise epithelium homeostasis. 6,8 The exact mechanisms by which H19 regulates Paneth and goblet cell levels remain unknown and are under intensive investigation in our laboratory.…”

“…33 Deficiency of autophagy proteins and/or reduction in autophagy also reduced Paneth and goblet cell levels and function. 6,8,50,51 Defective autophagy is observed commonly in mice with destructive mucosal inflammatory erosions, 51 and disrupted expression of autophagy genes such as Atg16l1, Atg5, and Atg7 also occurs in patients with inflammatory bowel diseases and other mucosal disorders. 6,50 Although H19 deletion activates autophagy in the intestinal epithelium, the exact mechanisms and consequences of the altered autophagic response in Paneth and goblet cell function remain be investigated using appropriate mouse models.…”

“…Isolation and culture of primary enterocytes were conducted following the method described previously. 8,56 Briefly, primary crypts were released from the small intestinal mucosa in mice, then the isolated crypts were mixed with Matrigel (Corning Inc, Corning, NY) and cultured in Advanced Dulbecco's modified Eagle medium/F12 medium. The growth of organoids was examined under phasecontrast microscopy.…”