Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare and complex disease defined by congenital aplasia of the vagina and uterus in 46,XX women, often associated with kidney and urinary tract anomalies. The aetiopathogenesis of MRKH syndrome is still largely unknown. Herein, we investigated the role of selected candidate genes in the aetiopathogenesis of MRKH syndrome, with a focus on PRKX, which encodes for protein kinase X. Through RT-qPCR analyses performed on vaginal dimple samples from patients, and principal component analysis (PCA), we highlighted a phenotype-related expression pattern of PRKX, MUC1, HOXC8 and GREB1L in MRKH patients. By using an in vitro approach, we proved that PRKX ectopic overexpression in a cell model of vaginal keratinocytes promotes cell motility through epithelial-to-mesenchymal transition (EMT) activation, a fundamental process in urogenital tract morphogenesis. Moreover, our findings showed that PRKX upregulation in vaginal keratinocytes is able to affect transcriptional levels of HOX genes, implicated in urinary and genital tract development. Our study identified the dysregulation of PRKX expression as a possible molecular cause for MRKH syndrome. Moreover, we propose the specific role of PRKX in vaginal keratinocyte biology as one of the possible mechanisms underlying this complex disease.

Altered expression of candidate genes in Mayer–Rokitansky–Küster–Hauser syndrome may influence vaginal keratinocytes biologya. A focus on Protein Kinase X / Pontecorvi, P.; Megiorni, F.; Camero, S.; Ceccarelli, S.; Bernardini, L.; Capalbo, A.; Anastasiadou, E.; Gerini, G.; Messina, E.; Perniola, G.; Panici, P. B.; Grammatico, P.; Pizzuti, A.; Marchese, C.. - In: BIOLOGY. - ISSN 2079-7737. - 10:6(2021), pp. 1-22. [10.3390/biology10060450]

Altered expression of candidate genes in Mayer–Rokitansky–Küster–Hauser syndrome may influence vaginal keratinocytes biologya. A focus on Protein Kinase X

Pontecorvi P.;Megiorni F.;Camero S.;Ceccarelli S.;Anastasiadou E.;Gerini G.;Messina E.;Perniola G.;Panici P. B.;Grammatico P.;Pizzuti A.;Marchese C.
2021

Abstract

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare and complex disease defined by congenital aplasia of the vagina and uterus in 46,XX women, often associated with kidney and urinary tract anomalies. The aetiopathogenesis of MRKH syndrome is still largely unknown. Herein, we investigated the role of selected candidate genes in the aetiopathogenesis of MRKH syndrome, with a focus on PRKX, which encodes for protein kinase X. Through RT-qPCR analyses performed on vaginal dimple samples from patients, and principal component analysis (PCA), we highlighted a phenotype-related expression pattern of PRKX, MUC1, HOXC8 and GREB1L in MRKH patients. By using an in vitro approach, we proved that PRKX ectopic overexpression in a cell model of vaginal keratinocytes promotes cell motility through epithelial-to-mesenchymal transition (EMT) activation, a fundamental process in urogenital tract morphogenesis. Moreover, our findings showed that PRKX upregulation in vaginal keratinocytes is able to affect transcriptional levels of HOX genes, implicated in urinary and genital tract development. Our study identified the dysregulation of PRKX expression as a possible molecular cause for MRKH syndrome. Moreover, we propose the specific role of PRKX in vaginal keratinocyte biology as one of the possible mechanisms underlying this complex disease.
cell migration; emt; gene expression; genital tract development; hox genes; mayer–rokitansky–küster–hauser syndrome; prkx; tissue morphogenesis; vaginal keratinocyte
01 Pubblicazione su rivista::01a Articolo in rivista
Altered expression of candidate genes in Mayer–Rokitansky–Küster–Hauser syndrome may influence vaginal keratinocytes biologya. A focus on Protein Kinase X / Pontecorvi, P.; Megiorni, F.; Camero, S.; Ceccarelli, S.; Bernardini, L.; Capalbo, A.; Anastasiadou, E.; Gerini, G.; Messina, E.; Perniola, G.; Panici, P. B.; Grammatico, P.; Pizzuti, A.; Marchese, C.. - In: BIOLOGY. - ISSN 2079-7737. - 10:6(2021), pp. 1-22. [10.3390/biology10060450]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1556834
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