A novel tonicity-responsive microRNA miR-23a-5p modulates renal cell survival under osmotic stress through targeting heat shock protein 70 HSPA1B

2020 ◽  
Author(s):  
Kang Kang ◽  
Xiaoyun Liao ◽  
Qing Li ◽  
Jidong Chen ◽  
Yanqin Niu ◽  
...  
Keyword(s):  
Heat Shock ◽  
Osmotic Stress ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Collecting Duct ◽  
Luciferase Assay ◽  
Cellular Adaptation ◽  
Hypertonic Stress ◽  
Passenger Strand

There is growing evidence that microRNAs (miRNAs) are implicated in cellular adaptation to osmotic stress, but the underlying osmosignaling pathways are still not completely understood. In this study, we found that a passenger strand miRNA miR-23a-5p was significantly down-regulated in response to high NaCl treatment in mouse inner medullary collecting duct cells (mIMCD3) through a miRNA profiling assay. The decrease of miR-23a-5p is hypertonicity-dependent and osmotolerant cell type-specific. Knockdown of miR-23a-5p increased cellular survival and proliferation in mIMCD3. In contrast, miR-23a-5p overexpression repressed cell viability and proliferation under hypertonic stress. RNA deep-sequencing revealed that a heat shock protein 70 (HSP70) isoform, HSP70 member 1B (HSPA1B), was significantly increased under hypertonic treatment. Based on the prediction analysis by Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and TargetScan, and a further validation via a dual-luciferase assay, HSPA1B was identified as a potential target of miR-23a-5p. Overexpressed miR-23a-5p suppressed HSPA1B while down-regulated miR-23a-5p promoted HSPA1B expression in mIMCD3. In addition, an in vivo study demonstrated that there is a reverse correlation between the levels of miR-23a-5p and HSPA1B in mouse renal inner medulla (papilla) that is exposed to extremely high osmolality. In summary, this study elucidates that passenger strand miR-23a-5p is a novel tonicity-responsive miRNA. The down-regulation of miR-23a-5p facilitates cellular adaptation to hypertonic stress in mammalian renal cells through modulating HSPA1B.

scholarly journals Επικεκαλυμμένες ενδαγγειακές προθέσεις και επαναστένωση μετά από αγγειοπλαστική

2014 ◽  
Author(s):  
Δημήτριος Λυσίτσας
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Low Dose ◽  
High Dose ◽  
Hsp 70

Εισαγωγή: Η υπερπλασία του έσω χιτώνα παίζει μείζων ρόλο στην επαναστένωση (in-stentrestenosis). Στην παρούσα μελέτη αξιολογήσαμε in vitro την επίδραση της D-24851(κυτταροτοξική ουσία που σταματά τον κυτταρικό κύκλο στο στάδιο G2-M) στονπολλαπλασιασμό των λείων μυϊκών κυττάρων και μελετήσαμε την ασφάλεια και τηνδραστικότητα μίας ενδαγγειακής πρόθεσης (stent) επικαλυμμένης με πολυμερή ουσία πουαπελευθερώνει την D-24851, στην αναστολή της υπερπλασίας του έσω χιτώνα χωρίς ναεμποδίζει την αναγεννητική ικανότητα του ενδοθηλίου σε in vivo πειραματικό μοντέλο.Υλικό και Μέθοδοι: Γυμνά μεταλλικά stent (n=6), stent επικαλυμμένα μόνο με πολυμερήουσία (polymer-coated, n=7) και stent επικαλυμμένα με πολυμερή ουσία πουαπελευθερώνουν 31±1μg (low-dose, n=7), 216±8 μg (high-dose, n=6) ή 1774±39 μg(extreme-dose, n=5) της D-24851 εμφυτεύτηκαν στις μηριαίες αρτηρίες λευκών New Zealandκουνελιών. Τα πειραματόζωα θυσιάστηκαν στις 28 ημέρες για ιστομορφομετρική ανάλυση.Για την αξιολόγηση της ενδοθηλιακής αναγέννησης στις 90 ημέρες, 12 πειραματόζωαχρησιμοποιήθηκαν για την τοποθέτηση polymer-coated (n=3), low dose (n=3), high dose(n=3) or extreme dose (n=3) ενδαγγειακών προθέσεων.Αποτελέσματα: In vitro η D-24851 αναστέλλει την υπερπλασία των λείων μυϊκών κυττάρωνκαι επάγει την απόπτωση τους χωρίς να αυξάνει την επαγωγή της heat shock protein 70(HSP-70), μία κυτταροπροστατευτική και αντι-αποπτωτική πρωτεΐνη. Η θεραπεία με lowdoseD-24851 stents συνδυάστηκε με 38% (P=0.029) μείωση της υπερπλαστικής περιοχήςτου έσω χιτώνα και 35% (P=0.003) μείωση της επι τοις εκατό στένωσης του αυλού σεσύγκριση με τα γυμνά μεταλλικά stents. Ο τραυματισμός και η φλεγμονή του αρτηριακού τοιχώματος δεν παρουσίασαν σημαντικές διαφορές μεταξύ των ομάδων. Τα επικαλυμμέναμόνο με πολυμερή ουσία stents εμφάνισαν παρόμοια ανάπτυξη νεοιστού σε σύγκριση με ταγυμνά μεταλλικά stents. Ωστόσο, όλες οι ομάδες των stents με D-24851 παρουσίασαν ατελήενδοθηλιοποίηση συγκρινόμενα με τα polymer-coated stents.Συμπεράσματα: Οι επικεκαλυμμένες ενδαγγειακές προσθέσεις με πολυμερή ουσία καιχαμηλη δόση D-24851 μειώνουν σημαντικά την υπερπλασιά του έσω χιτώνα. Λόγω τηςατελούς ενδοθηλιοποίησης, μακράς διάρκειας μελέτες είναι απαραίτητες για ναπιστοποιήσουν ότι η αναστολή του νεοιστού παραμένει και μετά τις 28 ημέρες.

Heat shock protein 70 / MAGE-1 tumor vaccine can enhance the potency of MAGE-1–specific cellular immune responses in vivo

2004 ◽  
Vol 53 (9) ◽  
pp. 825-834 ◽  
Author(s):  
Jing Ye ◽  
Guang-Sheng Chen ◽  
Hong-Ping Song ◽  
Zeng-Shan Li ◽  
Ya-Yu Huang ◽  
...  
Keyword(s):  
Heat Shock ◽  
Immune Responses ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Tumor Vaccine ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals In Vivo Chaperone Activity of Heat Shock Protein 70 and Thermotolerance

1999 ◽  
Vol 19 (3) ◽  
pp. 2069-2079 ◽  
Author(s):  
Ellen A. A. Nollen ◽  
Jeanette F. Brunsting ◽  
Han Roelofsen ◽  
Lee A. Weber ◽  
Harm H. Kampinga
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Resistance ◽  
Cell Line ◽  
Heat Shock Protein 70 ◽  
Chaperone Activity ◽  
Luciferase Reporter ◽  
Reporter Protein ◽  
Regulated Gene Expression

ABSTRACT Heat shock protein 70 (Hsp70) is thought to play a critical role in the thermotolerance of mammalian cells, presumably due to its chaperone activity. We examined the chaperone activity and cellular heat resistance of a clonal cell line in which overexpression of Hsp70 was transiently induced by means of the tetracycline-regulated gene expression system. This single-cell-line approach circumvents problems associated with clonal variation and indirect effects resulting from constitutive overexpression of Hsp70. The in vivo chaperone function of Hsp70 was quantitatively investigated by using firefly luciferase as a reporter protein. Chaperone activity was found to strictly correlate to the level of Hsp70 expression. In addition, we observed an Hsp70 concentration dependent increase in the cellular heat resistance. In order to study the contribution of the Hsp70 chaperone activity, heat resistance of cells that expressed tetracycline-regulated Hsp70 was compared to thermotolerant cells expressing the same level of Hsp70 plus all of the other heat shock proteins. Overexpression of Hsp70 alone was sufficient to induce a similar recovery of cytoplasmic luciferase activity, as does expression of all Hsps in thermotolerant cells. However, when the luciferase reporter protein was directed to the nucleus, expression of Hsp70 alone was not sufficient to yield the level of recovery observed in thermotolerant cells. In addition, cells expressing the same level of Hsp70 found in heat-induced thermotolerant cells containing additional Hsps showed increased resistance to thermal killing but were more sensitive than thermotolerant cells. These results suggest that the inducible form of Hsp70 contributes to the stress-tolerant state by increasing the chaperone activity in the cytoplasm. However, its expression alone is apparently insufficient for protection of other subcellular compartments to yield clonal heat resistance to the level observed in thermotolerant cells.

scholarly journals In vivo analysis of heat-shock-protein-70 induction following pulsed laser irradiation in a transgenic reporter mouse

2008 ◽  
Vol 13 (3) ◽  
pp. 030501 ◽  
Author(s):  
Caitlin E. O’Connell-Rodwell ◽  
Mark A. Mackanos ◽  
Dmitri Simanovskii ◽  
Yu-An Cao ◽  
Michael H. Bachmann ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Laser Irradiation ◽  
Heat Shock Protein 70 ◽  
Pulsed Laser ◽  
Reporter Mouse ◽  
In Vivo Analysis ◽  
Pulsed Laser Irradiation

Differential Neuroprotection from Human Heat Shock Protein 70 Overexpression in in Vitro and in Vivo Models of Ischemia and Ischemia-like Conditions

2001 ◽  
Vol 170 (1) ◽  
pp. 129-139 ◽  
Author(s):  
Jong Eun Lee ◽  
Midori A. Yenari ◽  
Guo Hua Sun ◽  
Lijun Xu ◽  
Michelle R. Emond ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
In Vivo Models ◽  
Human Heat Shock Protein

scholarly journals The Adjuvant Effects of Mycobacterium tuberculosis Heat Shock Protein 70 Result from the Rapid and Prolonged Activation of Antigen-Specific CD8+ T Cells In Vivo

2002 ◽  
Vol 169 (10) ◽  
pp. 5622-5629 ◽  
Author(s):  
Lisa A. E. Harmala ◽  
Elizabeth G. Ingulli ◽  
Julie M. Curtsinger ◽  
Michelle M. Lucido ◽  
Clint S. Schmidt ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cd8 T Cells ◽  
Heat Shock Protein 70 ◽  
Adjuvant Effects

scholarly journals Human recombinant heat shock protein 70 affects the maturation pathways of dendritic cells in vitro and has an in vivo adjuvant activity

2008 ◽  
Vol 84 (1) ◽  
pp. 199-206 ◽  
Author(s):  
Barbara Valentinis ◽  
Annalisa Capobianco ◽  
Francesca Esposito ◽  
Alessandro Bianchi ◽  
Patrizia Rovere-Querini ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Adjuvant Activity

scholarly journals Localization and expression of heat shock protein 70 with rat myocardial cell damage induced by heat stress in vitro and in vivo

2014 ◽  
Vol 11 (3) ◽  
pp. 2276-2284 ◽  
Author(s):  
HONGBO CHEN ◽  
ABDELNASIR ADAM ◽  
YANFEN CHENG ◽  
SHU TANG ◽  
JÖRG HARTUNG ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Cell Damage ◽  
Myocardial Cell ◽  
Myocardial Cell Damage
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