RESUMO
The ability of adult vertebrates to repair tissue damage is widespread and impressive; however, the ability to regenerate structurally complex organs such as the limb is limited largely to the salamanders. The fact that most of the tissues of the limb can regenerate has led investigators to question and identify the barriers to organ regeneration. From studies in the salamander, it is known that one of the earliest steps required for successful regeneration involves signaling between nerves and the wound epithelium/apical epithelial cap (AEC). In this study we confirm an earlier report that the keratinocytes of the AEC acquire their function coincident with exiting the cell cycle. We have discovered that this unique, coordinated behavior is regulated by nerve signaling and is associated with the presence of gap junctions between the basal keratinocytes of the AEC. Disruption of nerve signaling results in a loss of gap junction protein, the reentry of the cells into the cell cycle, and regenerative failure. Finally, coordinated exit from the cell cycle appears to be a conserved behavior of populations of cells that function as signaling centers during both development and regeneration.
Assuntos
Ambystoma mexicanum/fisiologia , Epitélio/fisiologia , Queratinócitos/citologia , Transdução de Sinais , Animais , Proliferação de Células , Epitélio/inervação , Queratinócitos/fisiologia , Tecido Nervoso/fisiologia , RegeneraçãoRESUMO
Background/Aim: Short-circuit current (Isc) and transepithelial potential difference (PD) of rat distal colon decrease during acute hypoxia and overshoot on reoxygenation. It is not known whether tonic intrinsic nervous activity may influence these responses. Methods: Preparations lacking the submucosal plexus (isolet mucosa) and preparations retaining it (mucosa-submucosa) were mounted in Ussing chambers at 37 degrees Celsius and gassed with 95 percent O2 -5 percent CO2; Isc and PD were monitored. A 5-min hypoxia with 95 percent N2-5 percent CO2 was followed by reoxygenation. The procedure was repeated in the presence of the nervous blocking agent, tetrodotoxin (10(-6)M) in the serosal side of the chamber. Results: In the isolated mucosa (n=10) hypoxia reduced Isc by -55 + 5 percent and PD by -54 + 6 percent below baseline; reoxygenatory overschoots were, respectively, + 60 + 17 percent and + 16 percent. Tetrodotoxin slightly and transiently reduced baseline Isc (-16 + 2 percent) and PD (-14 + 3 percent), with a small resistivity increase. It did not significatively modify the responses to responses to either hypoxia or reoxygenation. In mucosa-submucosa preparations (n=9) hypoxia reduced Isc (-54 + 8 percent) and PD (-61 + 4 percent). On reoxygenation Isc and PD were increased, respectively, +30 + 5 percent and +19 + 6 percent over baseline. Tetrodotoxin reduced baseline Isc (-59,6 + 5 percent) and PD (61,3 + 6 percent). It enhanced hypoxic Isc and PD decreases (-80 + 5 percent), but not the reoxygenatory overschoots. Conclusions: 1) Tetrodotoxin affects baseline Isc and PD more intensely in submucosal plexus innervated preparations than in the isolated mucosa. 2) The epithelial electrical response to acute hypoxia appears to be modulated by tonic neural activity.
Assuntos
Ratos , Animais , Masculino , Colo/inervação , Hipóxia/metabolismo , Plexo Submucoso/metabolismo , Tetrodotoxina/farmacologia , Doença Aguda , Colo/efeitos dos fármacos , Colo/metabolismo , Eletrofisiologia , Epitélio/inervação , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/inervação , Mucosa Intestinal/metabolismo , Ratos WistarRESUMO
Background/Aim: Short-circuit current (Isc) and transepithelial potential difference (PD) of rat distal colon decrease during acute hypoxia and overshoot on reoxygenation. It is not known whether tonic intrinsic nervous activity may influence these responses. Methods: Preparations lacking the submucosal plexus (isolet mucosa) and preparations retaining it (mucosa-submucosa) were mounted in Ussing chambers at 37 degrees Celsius and gassed with 95 percent O2 -5 percent CO2; Isc and PD were monitored. A 5-min hypoxia with 95 percent N2-5 percent CO2 was followed by reoxygenation. The procedure was repeated in the presence of the nervous blocking agent, tetrodotoxin (10(-6)M) in the serosal side of the chamber. Results: In the isolated mucosa (n=10) hypoxia reduced Isc by -55 + 5 percent and PD by -54 + 6 percent below baseline; reoxygenatory overschoots were, respectively, + 60 + 17 percent and + 16 percent. Tetrodotoxin slightly and transiently reduced baseline Isc (-16 + 2 percent) and PD (-14 + 3 percent), with a small resistivity increase. It did not significatively modify the responses to responses to either hypoxia or reoxygenation. In mucosa-submucosa preparations (n=9) hypoxia reduced Isc (-54 + 8 percent) and PD (-61 + 4 percent). On reoxygenation Isc and PD were increased, respectively, +30 + 5 percent and +19 + 6 percent over baseline. Tetrodotoxin reduced baseline Isc (-59,6 + 5 percent) and PD (61,3 + 6 percent). It enhanced hypoxic Isc and PD decreases (-80 + 5 percent), but not the reoxygenatory overschoots. Conclusions: 1) Tetrodotoxin affects baseline Isc and PD more intensely in submucosal plexus innervated preparations than in the isolated mucosa. 2) The epithelial electrical response to acute hypoxia appears to be modulated by tonic neural activity. (AU)