Altered Expression Pattern of Molecular Factors Involved in Colonic Smooth Muscle Functions: An Immunohistochemical Study in Patients with Diverticular Disease

Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia

doi:10.1371/journal.pone.0057023

Cited by 31 publications

(24 citation statements)

References 45 publications

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“…Immunohistochemical studies indicate that Cx26, Cx32 and Cx43 are expressed at the protein level in the normal colon in humans . The connexins localize in intracellular compartments, but also in distinct, punctuate plasma membrane domains likely representing gap junctions.…”

Section: Expression Of Connexins In the Normal Colonmentioning

confidence: 99%

“…Immunohistochemical studies indicate that Cx26, Cx32 and Cx43 are expressed at the protein level in the normal colon in humans. [77][78][79][80][81][82][83] The connexins localize in intracellular compartments, but also in distinct, punctuate plasma membrane domains likely representing gap junctions. The notion that connexins are able to form gap junctions in normal colonic mucosa is further supported by Western blot analysis of protein extracts from normal colon tissue.…”

Section: Expression Of Connexins In the Normal Colonmentioning

confidence: 99%

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Connexins in colorectal cancer pathogenesis

Sirnes

Lind

Bruun

et al. 2014

Intl Journal of Cancer

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The connexins constitute a family of integral membrane proteins that form channels between adjacent cells. These channels are assembled in plasma membrane domains known as gap junctions and enable cells to directly exchange ions and small molecules. Intercellular communication via gap junctions plays important roles in regulating cell growth and differentiation and in maintaining tissue homeostasis. This type of cell communication is often impaired during cancer development, and several members of the connexin protein family have been shown to act as tumor suppressors. Emerging evidence suggests that the connexin protein family has important roles in colorectal cancer development. In the normal colonic epithelial tissue, three connexin isoforms, connexin 26 (Cx26), Cx32 and Cx43, have been shown to be expressed at the protein level. Colorectal cancer development is associated with loss of connexin expression or relocalization of connexins from the plasma membrane to intracellular compartments. Downregulation of connexins in colorectal carcinomas at the transcriptional level involves cancerspecific promoter hypermethylation. Recent studies suggest that Cx43 may constrain growth of colon cancer cells by interfering with the Wnt/b-catenin pathway. There is also increasing evidence that the connexins may have potential as prognostic markers in colorectal cancer. This review discusses the role of connexins in colorectal cancer pathogenesis, as well as their potential as prognostic markers and targets in the prevention and treatment of the disease.

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Section: Expression Of Connexins In the Normal Colonmentioning

confidence: 99%

Section: Expression Of Connexins In the Normal Colonmentioning

confidence: 99%

Connexins in colorectal cancer pathogenesis

Sirnes

Lind

Bruun

et al. 2014

Intl Journal of Cancer

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“…Thus, symptoms related to abnormal (hypercontractile) patterns of colonic motor functions in DD patients might depend, at least in part, upon the alterations highlighted in our study. Of course, other abnormalities, such as those related to colonic smooth muscle (Mattii et al, 2013) and mast cells within the colonic layers (Bassotti et al, 2013), are likely also to play pathophysiological roles, and it is possible that the summation of different abnormalities leads to the generation of dysmotilityrelated (Bassotti and Villanacci, 2012) and sensory (Clemens et al, 2004) abdominal symptoms often reported by patients with DD.…”

Section: Figurementioning

confidence: 99%

“…Notably, DD has been associated also with neuromuscular dysfunctions (Bassotti et al, 2001;Bassotti and Villanacci, 2012). Colonic motor abnormalities in DD have been hypothesized to result from changes in enteric nerves, smooth muscle functions (Golder et al, 2003;Bassotti et al, 2005a;Mattii et al, 2013), and low-grade mucosal and myenteric inflammation (Bassotti et al, 2013). In addition, alterations in the excitatory control by enteric cholinergic nerves have been observed in DD, but not by all groups (Tomita et al, 2000;Golder et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease

Fornai

Colucci

Antonioli

et al. 2014

British J Pharmacology

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Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol-and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. KEY RESULTSIn control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. CONCLUSIONS AND IMPLICATIONSIn control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity. AbbreviationsDD, diverticular disease; PPP, percent positive pixels; SP, substance P BJP British Journal of Pharmacology

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“…Cx26 has been described in a number of tissues but not in the heart and its mutations are frequently associated with deafness and skin diseases 6 , 7 . An altered expression of Cx26 in colonic smooth muscle cells may predispose the formation of diverticular lesions 8 while the reduced expression of Cx26 may contribute to the low sensitivity of hepatocellular carcinoma towards the chemotherapeutic agent oxaliplatin 9 .…”

Section: Introductionmentioning

confidence: 99%

Connexin 26 Expression in Mammalian Cardiomyocytes

Moscato

Cabiati

Bianchi

et al. 2018

Sci Rep

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Connexins are a family of membrane-spanning proteins named according to their molecular weight. They are known to form membrane channels mediating cell-cell communication, which play an essential role in the propagation of electrical activity in the heart. Cx26 has been described in a number of tissues but not in the heart, and its mutations are frequently associated with deafness and skin diseases. The aim of this study was to assess the possible Cx26 expression in heart tissues of different mammalian species and to demonstrate its localization at level of cardiomyocytes. Samples of pig, human and rat heart and H9c2 cells were used for our research. Immunohistochemical and molecular biology techniques were employed to test the expression of Cx26. Interestingly, this connexin was found in cardiomyocytes, at level of clusters scattered over the cell cytoplasm but not at level of the intercalated discs where the other cardiac connexins are usually located. Furthermore, the expression of Cx26 in H9c2 myoblast cells increased when they were differentiated into cardiac-like phenotype. To our knowledge, the expression of Cx26 in pig, human and rat has been demonstrated for the first time in the present paper.

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Altered Expression Pattern of Molecular Factors Involved in Colonic Smooth Muscle Functions: An Immunohistochemical Study in Patients with Diverticular Disease

Cited by 31 publications

References 45 publications

Connexins in colorectal cancer pathogenesis

Connexins in colorectal cancer pathogenesis

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease

Connexin 26 Expression in Mammalian Cardiomyocytes

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