PMID- 25521239 OWN - NLM STAT- MEDLINE DCOM- 20150831 LR - 20181113 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 19 IP - 2 DP - 2015 Feb TI - An integrated assessment of histopathological changes of the enteric neuromuscular compartment in experimental colitis. PG - 485-500 LID - 10.1111/jcmm.12428 [doi] AB - Bowel inflammatory fibrosis has been largely investigated, but an integrated assessment of remodelling in inflamed colon is lacking. This study evaluated tissue and cellular changes occurring in colonic wall upon induction of colitis, with a focus on neuromuscular compartment. Colitis was elicited in rats by 2,4-dinitrobenzenesulfonic acid (DNBS). After 6 and 21 days, the following parameters were assessed on paraffin sections from colonic samples: tissue injury and inflammatory infiltration by histology; collagen and elastic fibres by histochemistry; HuC/D, glial fibrillar acidic protein (GFAP), proliferating cell nuclear antigen (PCNA), nestin, substance P (SP), von Willebrand factor, c-Kit and transmembrane 16A/Anoctamin1 (TMEM16A/ANO1) by immunohistochemistry. TMEM16A/ANO1 was also examined in isolated colonic smooth muscle cells (ICSMCs). On day 6, inflammatory alterations and fibrosis were present in DNBS-treated rats; colonic wall thickening and fibrotic remodelling were evident on day 21. Colitis was associated with both an increase in collagen fibres and a decrease in elastic fibres. Moreover, the neuromuscular compartment of inflamed colon displayed a significant decrease in neuron density and increase in GFAP/PCNA-positive glia of myenteric ganglia, enhanced expression of neural SP, blood vessel remodelling, reduced c-Kit- and TMEM16A/ANO1-positive interstitial cells of Cajal (ICCs), as well as an increase in TMEM16A/ANO1 expression in muscle tissues and ICSMCs. The present findings provide an integrated view of the inflammatory and fibrotic processes occurring in the colonic neuromuscular compartment of rats with DNBS-induced colitis. These morphological alterations may represent a suitable basis for understanding early pathophysiological events related to bowel inflammatory fibrosis. CI - (c) 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Ippolito, Chiara AU - Ippolito C AD - Unit of Histology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Segnani, Cristina AU - Segnani C FAU - Errede, Mariella AU - Errede M FAU - Virgintino, Daniela AU - Virgintino D FAU - Colucci, Rocchina AU - Colucci R FAU - Fornai, Matteo AU - Fornai M FAU - Antonioli, Luca AU - Antonioli L FAU - Blandizzi, Corrado AU - Blandizzi C FAU - Dolfi, Amelio AU - Dolfi A FAU - Bernardini, Nunzia AU - Bernardini N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141217 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 SB - IM MH - Animals MH - Colitis/*pathology MH - Colon/pathology MH - Inflammation/pathology MH - Male MH - Myocytes, Smooth Muscle/*pathology MH - Rats MH - Rats, Sprague-Dawley PMC - PMC4407593 OTO - NOTNLM OT - DNBS OT - colonic inflammatory fibrosis OT - myenteric ganglia OT - neuromuscular compartment OT - wall remodelling EDAT- 2014/12/19 06:00 MHDA- 2015/09/01 06:00 PMCR- 2015/02/01 CRDT- 2014/12/19 06:00 PHST- 2013/07/26 00:00 [received] PHST- 2014/08/14 00:00 [accepted] PHST- 2014/12/19 06:00 [entrez] PHST- 2014/12/19 06:00 [pubmed] PHST- 2015/09/01 06:00 [medline] PHST- 2015/02/01 00:00 [pmc-release] AID - 10.1111/jcmm.12428 [doi] PST - ppublish SO - J Cell Mol Med. 2015 Feb;19(2):485-500. doi: 10.1111/jcmm.12428. Epub 2014 Dec 17.