Cellular Factor XIII, a Transglutaminase in Human Corneal Keratocytes

Zsuzsanna Z Orosz; Helga Bárdos; Amir H Shemirani; Ildikó Beke Debreceni; Riitta Lassila; Antti S Riikonen; Johanna A Kremer Hovinga; Theo G Seiler; Hendrika A van Dorland; Verena Schroeder; Zoltán Boda; László Nemes; Beatrice Früh Eppstein; Bence Nagy; Andrea Facskó; János Kappelmayer; László Muszbek

doi:10.3390/ijms20235963

Cellular Factor XIII, a Transglutaminase in Human Corneal Keratocytes

Int J Mol Sci. 2019 Nov 27;20(23):5963. doi: 10.3390/ijms20235963.

Authors

Zsuzsanna Z Orosz^{1

2}, Helga Bárdos³, Amir H Shemirani¹, Ildikó Beke Debreceni⁴, Riitta Lassila⁵, Antti S Riikonen⁶, Johanna A Kremer Hovinga⁷, Theo G Seiler⁸, Hendrika A van Dorland⁷, Verena Schroeder⁹, Zoltán Boda¹⁰, László Nemes¹¹, Beatrice Früh Eppstein⁸, Bence Nagy¹², Andrea Facskó², János Kappelmayer⁴, László Muszbek¹

Affiliations

¹ Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Faculty of General Medicine, 4032 Debrecen, Hungary.
² Department of Ophthalmology, University of Szeged, 6720 Szeged, Hungary.
³ Department of Preventive Medicine, University of Debrecen, 4028 Debrecen, Hungary.
⁴ Department of Laboratory Medicine, University of Debrecen, Faculty of General Medicine, 4032 Debrecen, Hungary.
⁵ Coagulation Disorders Unit, Department of Hematology, Comprehensive Cancer Center, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.
⁶ Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
⁷ Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland.
⁸ Universitätsklinik für Augenheilkunde, Inselspital, Universität Bern, 3010 Bern, Switzerland.
⁹ Department for BioMedical Research (DBMR), Experimental Haemostasis Group, University of Bern, 3008 Bern, Switzerland.
¹⁰ Department of Internal Medicine, Thrombosis and Haemostasis Center, University of Debrecen, 4032 Debrecen, Hungary.
¹¹ National Haemophilia Center and Haemostasis Department, State Health Center, 1134 Budapest, Hungary.
¹² Department of Pathology, University of Szeged, 6270 Szeged, Hungary.

Abstract

Cellular factor XIII (cFXIII, FXIII-A₂), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea. Tissue sections of the cornea were immunostained for FXIII-A in combination with staining for CD34 antigen or isopeptide cross-links. Isolated corneal keratocytes were also evaluated by immunofluorescent microscopy and flow cytometry. FXIII-A in the corneal stroma was quantified by Western blotting. FXIII-A mRNA was detected by RT-qPCR. The cornea of FXIII-A-deficient patients was evaluated by cornea topography. FXIII-A was detected in 68 ± 13% of CD34+ keratocytes. Their distribution in the corneal stroma was unequal; they were most abundant in the subepithelial tertile. cFXIII was of cytoplasmic localization. In the stroma, 3.64 ng cFXIII/mg protein was measured. The synthesis of cFXIII by keratocytes was confirmed by RT-qPCR. Isopeptide cross-links were detected above, but not within the corneal stroma. Slight abnormality of the cornea was detected in six out of nine FXIII-A-deficient patients. The presence of cFXIII in human keratocytes was established for the first time. cFXIII might be involved in maintaining the stability of the cornea and in the corneal wound healing process.

Keywords: cornea; factor XIII; isopeptide bonds; keratocytes; transglutaminase.

MeSH terms

Blood Coagulation Tests / methods
Corneal Injuries / metabolism
Corneal Keratocytes / metabolism*
Corneal Stroma / metabolism*
Factor XIII / metabolism*
Humans
RNA, Messenger / metabolism
Transglutaminases / metabolism*
Wound Healing / physiology

Substances

RNA, Messenger
Factor XIII
Transglutaminases

Abstract

MeSH terms

Substances

Grants and funding