To the wound correlated with the extent of injury and occurred in two bands around the wound site. The position of the two bands of proliferation was within the region of the epithelium experiencing the most linear stretch secondary to cell migration. At the same time, we observed that injuring one tubule did not result in increased proliferation in the adjacent contralateral tubule. These results suggest that the signals regulating proliferation in response to injury are intrinsic to the injured tubule itself and support the idea that proliferation may be signaled by mechanical stretch produced by cell migration. The spatial and temporal resolution of our model also allows us to propose that Torin 1 collective cell migration is the primary response to tubule injury, occurring well before any significant cell proliferation can be detected. Further experiments measuring cell migration and the role of mechanical stretch directly in vivo or in in vitro cell culture models will be required to definitively link cell migration and cell proliferation during kidney repair and to identify the exact mechanical forces leading to increased cell proliferation. Another advantage of the photoablation methodology we present is that it allows graded amounts of photodamage to be applied, ranging from minimal, with no effect on cell survival to massive, resulting in cell necrosis. This gradual control is not possible using conventional photoablation techniques. In addition, the method takes advantage of tissue specific GFP expression and can be potentially applied to a very large number of GFP transgenic animals already available. The Killer red fluorescent protein based system has been shown to be similarly effective for cell ablation, but the number of available fish lines is relatively small compared to a number of GFP transgenics. In addition, the GFP- based system can be effectively used for both photoablation and subsequent imaging. This method may also be applicable in tissues outside the kidney. In a pilot experiment using 405 nm irradiation of heart cells expressing GFP under the control of the cmlc promoter, we were able to induce AV block by targeting cells around the AV canal. This result suggests that photosensitized cell death using GFP expression may have potential for in vivo cell ablation in kidney and some other organs. One of the major pathological features of the pancreas in type 2 diabetes is the presence of islet amyloid deposits, found in more than 80% of patients at autopsy. These deposits are implicated in the process of b-cell deterioration and reduction in beta-cell mass and involve islet amyloid polypeptide aggregation of monomers into oligomers, fibrils and, ultimately, mature amyloid deposits. The endoplasmic reticulum is the site of several important functions, including the synthesis, folding and maturation of secreted proteins. The pancreatic beta-cell has an extremely developed ER enabling the secretion of proteins such as insulin or IAPP. However, the accumulation of misfolded proteins can alter ER homeostasis.
As a consequence cells activate a succession of signal transduction cascades termed unfolded protein response
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