{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:59:24Z","timestamp":1760623164185,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04046\/2020","UIDP\/04046\/2020","PTDC\/BIM-MEC\/2131\/2014","PD\/BD\/106087\/2015","SFRH\/PD\/BD\/131008\/2017"],"award-info":[{"award-number":["UIDB\/04046\/2020","UIDP\/04046\/2020","PTDC\/BIM-MEC\/2131\/2014","PD\/BD\/106087\/2015","SFRH\/PD\/BD\/131008\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 013"],"award-info":[{"award-number":["SRC 013"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) cells display a more cancer-like phenotype vs. non-CF cells. KLF4 overexpression has been described in CF and this transcriptional factor acts as a negative regulator of wt-CFTR. KLF4 is described as exerting its effects in a cell-context-dependent fashion, but it is generally considered a major regulator of proliferation, differentiation, and wound healing, all the processes that are also altered in CF. Therefore, it is relevant to characterize the differential role of KLF4 in these processes in CF vs. non-CF cells. To this end, we used wt- and F508del-CFTR CFBE cells and their respective KLF4 knockout (KO) counterparts to evaluate processes like cell proliferation, polarization, and wound healing, as well as to compare the expression of several epithelial differentiation markers. Our data indicate no major impact of KLF4 KO in proliferation and a differential impact of KLF4 KO in transepithelial electrical resistance (TEER) acquisition and wound healing in wt- vs. F508del-CFTR cells. In parallel, we also observed a differential impact on the levels of some differentiation markers and epithelial-mesencymal transition (EMT)-associated transcription factors. In conclusion, KLF4 impacts TEER acquisition, wound healing, and the expression of differentiation markers in a way that is partially dependent on the CFTR-status of the cell.<\/jats:p>","DOI":"10.3390\/ijms21186717","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T09:04:53Z","timestamp":1600074293000},"page":"6717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Impact of KLF4 on Cell Proliferation and Epithelial Differentiation in the Context of Cystic Fibrosis"],"prefix":"10.3390","volume":"21","author":[{"given":"Lu\u00eds","family":"Sousa","sequence":"first","affiliation":[{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-7521","authenticated-orcid":false,"given":"Ines","family":"Pankonien","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2010-1282","authenticated-orcid":false,"given":"Filipa B.","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisbon, Portugal"}]},{"given":"Marc","family":"Chanson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Gynecology &amp; Obstetrics and of Cell Physiology &amp; Metabolism, Geneva University Hospitals and Medical School of the University of Geneva, 1211 Geneva, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0828-8630","authenticated-orcid":false,"given":"Margarida D.","family":"Amaral","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"ref_1","unstructured":"Zolin, A., Orenti, A., Naehrlich, L., and van Rens, J. 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