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Publication : Downregulation of CFTR Is Involved in the Formation of Hypertrophic Scars.

First Author  Zhou Y Year  2020
Journal  Biomed Res Int Volume  2020
Pages  9526289 PubMed ID  31998800
Mgi Jnum  J:296485 Mgi Id  MGI:6467859
Doi  10.1155/2020/9526289 Citation  Zhou Y, et al. (2020) Downregulation of CFTR Is Involved in the Formation of Hypertrophic Scars. Biomed Res Int 2020:9526289
abstractText  Hypertrophic Scars (HTSs) are a complex fibroproliferative disorder, and their exact mechanism is still not fully understood. In this study, we first found that cystic fibrosis transmembrane conductance regulator (CFTR) expression was downregulated in human hypertrophic scars at the RNA and protein levels by microarray data analysis, RT-PCR, and immunofluorescence (IF) staining. To validate that this downregulation of CFTR is involved in the formation of HTSs, we then applied a mechanical overloading intervention in both wild type and CFTR-mutant mice (DeltaF508). Our results showed thatDeltaF508 mice exhibited delayed wound healing and a significantly larger HTS on day 28. Masson staining revealed that there was more collagen deposition in the HTS, and Sirius red staining and IF staining showed a higher ratio of collagen 1/collagen 3 (Col1/Col3) in DeltaF508 mice. Real-time RT-PCR showed that the proinflammatory markers were higher in DeltaF508 mice in all phases of scar formation, whereas the proliferation marker was similar. Moreover, we harvested the fibroblasts from both mice. Western blotting showed that the expression of Col1 was the same in both mice, and the expression of Col3 was significantly lower in DeltaF508 mice. However, in a mechanical overloading condition, the expression of Col1 was significantly higher in DeltaF508 mice, and the expression of Col3 was the same in both mice. Taken together, our results indicate that the downregulation of CFTR might affect the function of fibroblasts, resulting in a lower level of collagen type 3 and a higher ratio of Col1/Col3, and thus aggravate the formation of HTSs in mechanical overloading conditions.
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