Proteolytic tailoring of the heat shock protein 70 and its implications in the pathogenesis of endometriosis

• Published in: Fertility and sterility Vol. 95; no. 5; pp. 1560 - 1567.e3
• Main Authors: Chehna-Patel, Nina, M.Sc, Warty, Neeta, M.D, Sachdeva, Geetanjali, Ph.D, Khole, Vrinda, Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2011; Elsevier
• Subjects: Adult; Base Sequence; Biological and medical sciences; ectopic; Endometriosis; Endometriosis - etiology; Endometriosis - genetics; Endometriosis - metabolism; Endometriosis - pathology; endometrium; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; heat-shock protein 70; HSP70; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Humans; IL-6; immunoblotting; inflammation; interleukin-6; Internal Medicine; isozymes; Medical sciences; Molecular Sequence Data; NF-κB; Non tumoral diseases; Obstetrics and Gynecology; pathogenesis; patients; Peritoneal Diseases - etiology; Peritoneal Diseases - genetics; Peritoneal Diseases - metabolism; Peritoneal Diseases - pathology; Proprotein Convertases - metabolism; proteases; Protein Processing, Post-Translational - physiology; proteolysis; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; regulatory proteins; reverse transcriptase polymerase chain reaction; Serine Endopeptidases - metabolism; SKI-1; subtilisin; Subtilisin - metabolism; Tissue Distribution; transcription factor NF-kappa B; Young Adult; NF-κB; SKI-1; HSP70; proteases; Endometriosis; ectopic; IL-6; B; Enzyme; Pathogenesis; Gynecology; Obstetrics; Female genital diseases; Interleukin 6; Peptidases; Heat shock protein; Uterine diseases; NF; Hydrolases; Ectopia; Transcription factor NFκB
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2011.01.122

Objective To investigate the mechanism underlying the appearance of a 20-kd HSP70 fragment and its consequences in the ectopic endometrium of endometriosis patients. Design Experimental study. Setting Research institute and obstetrics and gynecology clinic. Patient(s) Participants with (n = 18) and without (n = 20) endometriosis. Intervention(s) None. Main Outcome Measure(s) Reverse-transcription polymerase chain reaction, protease assays, and in silico tools were used to investigate the origin of the 20-kd HSP70 fragment. Immunocolocalization studies were carried out to determine whether subtilisin/kexin isozyme 1 (SKI-1) and HSP70 are colocalized. Expression and localization of surrogate markers of inflammation, such as nuclear factor NF-κB and interleukin IL-6 were examined by immunoblotting and in situ studies. Result(s) HSP70 is posttranslationally processed into a 20-kd fragment by SKI-1, a protease of the subtilisin family, in ectopic endometrium (ECE). Immunocolocalization studies revealed spatial proximity of SKI-1 and HSP70 in ECE. Furthermore, ECE demonstrated nuclear localization of the transcription factor, NF-κB and high expression of its target protein, IL-6. Conclusion(s) This study hints at the possible mechanisms underlying the trimming of HSP70 in ECE and also at the role of proteases in the pathogenesis of endometriosis. The possible repercussions of HSP70 fragmentation include dysregulation of key regulatory proteins, resulting in the escalation of inflammatory events in endometriotic lesions.