{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:52:24Z","timestamp":1792039944077,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. There is evidence that TGF-\u03b2 is intimately involved in the fibrogenic process. When activated, TGF-\u03b2 promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, \u03b1-SMA, Sphingosine-1, and TGF-\u03b21 tissue expression) involved in the TGF-\u03b21 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, \u03b1-SMA, Sphingosine-1, and TGF-\u03b21 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-\u03b2 pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-\u03b2 inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.<\/jats:p>","DOI":"10.3390\/ijms23010168","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T08:38:46Z","timestamp":1640335126000},"page":"168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["COVID-19: Immunohistochemical Analysis of TGF-\u03b2 Signaling Pathways in Pulmonary Fibrosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-8471","authenticated-orcid":false,"given":"Caroline Busatta","family":"Vaz de Paula","sequence":"first","affiliation":[{"name":"Postgraduate Program of Health Sciences, School of Medicine, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0069-3823","authenticated-orcid":false,"given":"Seigo","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Postgraduate Program of Health Sciences, School of Medicine, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Liberalesso","sequence":"additional","affiliation":[{"name":"Postgraduate Program of Health Sciences, School of Medicine, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-3397","authenticated-orcid":false,"given":"Mariana","family":"Collete","sequence":"additional","affiliation":[{"name":"Postgraduate Program of Health Sciences, School of Medicine, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-3281","authenticated-orcid":false,"given":"Felipe Paes Gomes","family":"da Silva","sequence":"additional","affiliation":[{"name":"Postgraduate Program of Health Sciences, School of Medicine, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9916-3069","authenticated-orcid":false,"given":"Alessandro Gon\u00e7alves Gomes","family":"Oricil","sequence":"additional","affiliation":[{"name":"Postgraduate Program of Health Sciences, School of Medicine, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-003X","authenticated-orcid":false,"given":"Giovanna Silva","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Postgraduate Program 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