JAK/STAT Dysregulation With SOCS1 Overexpression in Acquired Cholesteatoma-Adjacent Mucosa.

Autor:	Westerberg J; Department of Biomedical and Clinical Sciences, Division of Sensory Organs and Communication, Linköping University, Region Östergötland, Sweden., Tideholm E; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm., Piersiala K; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm.; Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden., Drakskog C; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm., Kumlien Georén S; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm., Mäki-Torkko E; Department of Biomedical and Clinical Sciences, Division of Sensory Organs and Communication, Linköping University, Region Östergötland, Sweden.; Audiological Research Center, Faculty of Medicine and Health, Örebro university, Sweden., Cardell LO; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm.; Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology [Otol Neurotol] 2021 Jan; Vol. 42 (1), pp. e94-e100.
DOI:	10.1097/MAO.0000000000002850
Abstrakt:	Importance: Surgery remains the gold standard in cholesteatoma treatment. However, the rate of recurrence is significant and the development of new nonsurgical treatment alternatives is warranted. One of the possible molecular pathways to target is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Objective: To investigate the JAK/STAT pathway in the middle ear mucosa in patients with acquired cholesteatoma compared with middle ear mucosa from healthy controls. Design: Case-control study. Setting: Linköping University Hospital, Sweden, and Karolinska Institutet, Stockholm, Sweden. Sampling period: February 2011 to December 2016. Participants: Middle ear mucosa from 26 patients with acquired cholesteatoma undergoing tympanoplasty and mastoidectomy, and 27 healthy controls undergoing translabyrinthine surgery for vestibular schwannoma or cochlear implantation was investigated. Main Outcomes/measures: The expression of Interleukin-7 receptor alpha, JAK1, JAK2, JAK3, STAT5A, STAT5B, and suppressor of cytokine signaling-1 (SOCS1) were quantified using quantitative polymerase chain reaction. In addition, expression level of cyclin D2, transforming growth factor beta 1, thymic stromal lymphopoietin, CD3, and CD19 was evaluated. Results: In cholesteatoma-adjacent mucosa, SOCS1 was significantly upregulated (p= 0.0003) compared with healthy controls, whereas STAT5B was significantly downregulated (p = 0.0006). The expression of JAK1, JAK2, JAK3, and STAT5A did not differ significantly between groups. Conclusions and Relevance: To the best of our knowledge, this is the first article reporting dysregulation of the JAK/STAT pathway in cholesteatoma-adjacent mucosa. The main finding is that important players of the aforementioned pathway are significantly altered, namely SOCS1 is upregulated and STAT5B is downregulated compared with healthy controls.
Databáze:	MEDLINE
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