MicroRNA-21-5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-318226
- Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.…
Autor(en): | Ann Kristin Reinhold, Susanne M. Krug, Ellaine Salvador, Reine S. Sauer, Franziska Karl-Schöller, Marzia Malcangio, Claudia Sommer, Heike L. Rittner |
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URN: | urn:nbn:de:bvb:20-opus-318226 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik |
Medizinische Fakultät / Neurologische Klinik und Poliklinik | |
Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004) | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Annals of the New York Academy of Sciences |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 1515 |
Heft / Ausgabe: | 1 |
Erste Seite: | 184 |
Letzte Seite: | 195 |
Originalveröffentlichung / Quelle: | Annals of the New York Academy of Sciences 2022, 1515(1):184-195. DOI: 10.1111/nyas.14816 |
DOI: | https://doi.org/10.1111/nyas.14816 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | CRPS; MMP9; RECK; blood nerve barrier; claudin-1; microRNA; neuropathic pain |
Datum der Freischaltung: | 04.07.2023 |
EU-Projektnummer / Contract (GA) number: | 602133 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |