Up-regulated FHL1 Expression Maybe Involved in the Prognosis of Hirschsprung's Disease

Abstract

Background: In a subset of patients with Hirschsprung's disease (HSCR), gastrointestinal motor dysfunction persisted long after surgical correction. Gastrointestinal motility is achieved through the coordinated activity of the enteric nervous system, interstitial cells of Cajal, and smooth muscle (SMC) cells. Inhibition of four-and-a-half LIM protein-1 (Fhl1) expression by siRNA significantly decreases pulmonary artery SMCs migration and proliferation. Furthermore when up-expressing FHL1 in atrial myocytes, K (+) current density markedly increases, therefore changing myocytes' response to an electrical stimulus. However whether FHL1 in colon SMCs (the final effector organ) influences intestinal motility in HSCR patients has not been clarified. Methods: FHL1 mRNA and protein expressions were analyzed in 32 HSCR colons and 4 normal colons. Results: Smooth muscle layers were thicken and disorganized in HSCR. FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 mRNA relative expression level in aganglionic colons was 1.06±0.49 (ganglionic colon relative expression level was 1) (P=0.44). FHL1 protein gray level relative to GAPDH in normal colons was 0.83±0.09. FHL1 expression level in ganglionic colon (1.66±0.30) or aganglionic colon (1.81±0.35) was significantly higher than that in normal colons (P=0.045 and P=0.041, respectively). Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon (P=0.036). Conclusion: These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction.

Lineage dynamics of murine pancreatic development at single-cell resolution

“…We utilized our single-cell mesenchymal dataset to determine whether the pancreatic mesothelium may function as a mesenchymal progenitor cell population during development. We found six populations (clusters 2, 3, 4, 5, 12, and 13) that expressed VSM cell genes, such as Acta2 and Tagln , or genes known to regulate VSM development, such as Mgp 20 , Fhl1 21 , 22 , Barx1 23 , and Pitx2 24 (Fig. 3d ).…”

Inhibition of FHL1 inhibits cigarette smoke extract-induced proliferation in pulmonary arterial smooth muscle cells

“…Previous studies have confirmed that FHL1 is highly expressed in skeletal muscle and in the heart (13,15), and is suggested to contribute to sarcomere synthesis, assembly and biomechanical stress sensing (16,17). Although considerably lower expression levels have been detected in several other tissue types, including colon, small intestine and prostate tissues (15), a previous study revealed that increased expression of FHL1 may be involved in the prognosis of Hirschsprung's disease (18). FHL1 deficiency was reported to significantly suppress proliferation, but exhibit no effect on the apoptosis of rat aortic SMCs (19).…”

NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF

“…Normal gastric emptying requires the coordinated function of the upper stomach fundus, lower body, antrum, and pylorus. [ 7 ] The gastrointestinal motility function and its regulation are accomplished via the collaboration and communication of extrinsic innervation to the stomach[ 7 ], enteric nerves, central nervous system[ 4 ], smooth muscle cells, interstitial cells of Cajal (ICCs)[ 8 ] and immune cells[ 7 ]. ICC was first described by the Spanish neuroanatomist Santiago Ramón y Cajal[ 9 ].…”