Identification of common sequence motifs shared exclusively among selectively packed exosomal pathogenic microRNAs during rickettsial infections

Jiani Bei, Yuan Qiu, Diane Cockrell, Qing Chang, Sorosh Husseinzadeh, Changcheng Zhou, Xiang Fang, Xiaoyong Bao, Yang Jin, Angelo Gaitas, Kamil Khanipov, Tais B. Saito, Bin Gong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia-infected endothelial cells (R-ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues. Therefore, the goal of the present study is to further dissect the molecular mechanism underlying R-ECExos-induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Infected ticks transmit the rickettsiae to human hosts following a bite and injections of the bacteria into the skin. In the present study, we demonstrate that treatment with R-ECExos, which were derived from spotted fever group R parkeri infected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE-cadherin, and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA-dependent manner. We did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy-relevant miR23a-27a-24 cluster and miR30b are selectively enriched in R-ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively-enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a monopartition, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy-relevant miR23a-27a-24 and miR30b, and subsequently results in their selective enrichments in R-ECExos.

Original languageEnglish
Pages (from-to)1937-1948
Number of pages12
JournalJournal of Cellular Physiology
Volume238
Issue number8
DOIs
StatePublished - Aug 2023

Keywords

  • endothelial barrier dysfunction
  • exosome
  • fluidic AFM
  • microRNA
  • rickettsial infection
  • sequence motif

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