Skip to main content
Erschienen in: Inflammation 4/2023

08.05.2023 | ORIGINAL ARTICLE

SOCS3 Silencing Promotes Activation of Vocal Fold Fibroblasts via JAK2/STAT3 Signaling Pathway

verfasst von: Xueyan Li, Rong Hu, Haizhou Wang, Wen Xu

Erschienen in: Inflammation | Ausgabe 4/2023

Einloggen, um Zugang zu erhalten

Abstract

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulatory protein that has been identified as a key inhibitory regulator of JAK/STAT signaling pathway. However, the mutual regulatory relationship between SOCS3 and JAK2/STAT3 signaling pathway after vocal fold injury remains unclear. In this study, we used small interfering RNA (siRNA) to investigate the mechanism of SOCS3 regulating of fibroblasts through JAK2/STAT3 signaling pathway after vocal fold injury. Our data shows that SOCS3 silencing promotes the transformation of normal vocal fold fibroblasts (VFFs) into an fibrotic phenotype and activates the JAK2/STAT3 signaling pathway. JAK2 silencing significantly inhibits the increase in type I collagen and α-smooth muscle actin (α-SMA) secretion in VFFs induced by TGF-β but has no significant effect on normal VFFs. The silencing of SOCS3 and JAK2 reverses the fibrotic phenotype of VFFs induced by SOCS3 silencing. Therefore, we suggest that SOCS3 can affect the activation of vocal fold fibroblasts by regulating the JAK2/STAT3 signaling pathway after vocal fold injury. It provides a new insight for promoting the repair of vocal fold injury and preventing the formation of fibrosis.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Meng, X.M., D.J. Nikolic-Paterson, and H.Y. Lan. 2016. TGF-beta: The master regulator of fibrosis. Nature Reviews. Nephrology 12 (6): 325–338.CrossRefPubMed Meng, X.M., D.J. Nikolic-Paterson, and H.Y. Lan. 2016. TGF-beta: The master regulator of fibrosis. Nature Reviews. Nephrology 12 (6): 325–338.CrossRefPubMed
2.
Zurück zum Zitat Kuzet, S., and C. Gaggioli. 2016. Fibroblast activation in cancer: When seed fertilizes soil. Cell and tissue research 365 (3): 607–619.CrossRefPubMed Kuzet, S., and C. Gaggioli. 2016. Fibroblast activation in cancer: When seed fertilizes soil. Cell and tissue research 365 (3): 607–619.CrossRefPubMed
3.
Zurück zum Zitat Zeisberg, E.M., and M. Zeisberg. 2013. The role of promoter hypermethylation in fibroblast activation and fibrogenesis. The Journal of Pathology 229 (2): 264–273.CrossRefPubMed Zeisberg, E.M., and M. Zeisberg. 2013. The role of promoter hypermethylation in fibroblast activation and fibrogenesis. The Journal of Pathology 229 (2): 264–273.CrossRefPubMed
4.
5.
Zurück zum Zitat Hu, R., et al. 2014. Characterization of extracellular matrix proteins during wound healing in the lamina propria of vocal fold in a canine model: A long-term and consecutive study. Acta Histochemica 116 (5): 730–735.CrossRefPubMed Hu, R., et al. 2014. Characterization of extracellular matrix proteins during wound healing in the lamina propria of vocal fold in a canine model: A long-term and consecutive study. Acta Histochemica 116 (5): 730–735.CrossRefPubMed
6.
Zurück zum Zitat Li, X., H. Wang, and W. Xu. 2022. HGF and bFGF secreted by adipose-derived mesenchymal stem cells revert the fibroblast phenotype caused by vocal fold injury in a rat model. Journal of Voice 36 (5): 622–629. Li, X., H. Wang, and W. Xu. 2022. HGF and bFGF secreted by adipose-derived mesenchymal stem cells revert the fibroblast phenotype caused by vocal fold injury in a rat model. Journal of Voice 36 (5): 622–629.
7.
Zurück zum Zitat Tang, S.S., et al. 2017. Insights into the role of collagen in vocal fold health and disease. Journal of Voice 31 (5): 520–527. Tang, S.S., et al. 2017. Insights into the role of collagen in vocal fold health and disease. Journal of Voice 31 (5): 520–527.
8.
Zurück zum Zitat Rockey, D.C., P.D. Bell, and J.A. Hill. 2015. Fibrosis–a common pathway to organ injury and failure. New England Journal of Medicine 372 (12): 1138–1149.CrossRefPubMed Rockey, D.C., P.D. Bell, and J.A. Hill. 2015. Fibrosis–a common pathway to organ injury and failure. New England Journal of Medicine 372 (12): 1138–1149.CrossRefPubMed
10.
Zurück zum Zitat Villarino, A.V., Y. Kanno, and J.J. O’Shea. 2017. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nature Immunology 18 (4): 374–384.CrossRefPubMed Villarino, A.V., Y. Kanno, and J.J. O’Shea. 2017. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nature Immunology 18 (4): 374–384.CrossRefPubMed
11.
Zurück zum Zitat Higgins, S.P., et al. 2018. TGF-beta1/p53 signaling in renal fibrogenesis. Cellular Signalling 43: 1–10.CrossRefPubMed Higgins, S.P., et al. 2018. TGF-beta1/p53 signaling in renal fibrogenesis. Cellular Signalling 43: 1–10.CrossRefPubMed
12.
Zurück zum Zitat Li, H., et al. 2018. Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway. BMC Complementary and Alternative Medicine 18 (1): 234.CrossRefPubMedPubMedCentral Li, H., et al. 2018. Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway. BMC Complementary and Alternative Medicine 18 (1): 234.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Shabbir, A., et al. 2010. Activation of host tissue trophic factors through JAK-STAT3 signaling: A mechanism of mesenchymal stem cell-mediated cardiac repair. American Journal of Physiology. Heart and Circulatory Physiology 299 (5): H1428–H1438.CrossRefPubMedPubMedCentral Shabbir, A., et al. 2010. Activation of host tissue trophic factors through JAK-STAT3 signaling: A mechanism of mesenchymal stem cell-mediated cardiac repair. American Journal of Physiology. Heart and Circulatory Physiology 299 (5): H1428–H1438.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Babon, J.J., et al. 2014. The molecular regulation of Janus kinase (JAK) activation. The Biochemical Journal 462 (1): 1–13.CrossRefPubMed Babon, J.J., et al. 2014. The molecular regulation of Janus kinase (JAK) activation. The Biochemical Journal 462 (1): 1–13.CrossRefPubMed
15.
Zurück zum Zitat Funakoshi-Tago, M., et al. 2017. Phosphorylated CIS suppresses the Epo or JAK2 V617F mutant-triggered cell proliferation through binding to EpoR. Cellular Signalling 31: 41–57.CrossRefPubMed Funakoshi-Tago, M., et al. 2017. Phosphorylated CIS suppresses the Epo or JAK2 V617F mutant-triggered cell proliferation through binding to EpoR. Cellular Signalling 31: 41–57.CrossRefPubMed
16.
Zurück zum Zitat Dees, C., et al. 2020. TGF-beta-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis. The Journal of Clinical Investigation 130 (5): 2347–2363.CrossRefPubMedPubMedCentral Dees, C., et al. 2020. TGF-beta-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis. The Journal of Clinical Investigation 130 (5): 2347–2363.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Eid, R.A., et al. 2019. A high-fat diet rich in corn oil induces cardiac fibrosis in rats by activating JAK2/STAT3 and subsequent activation of ANG II/TGF-1beta/Smad3 pathway: The role of ROS and IL-6 trans-signaling. Journal of Food Biochemistry 43 (8): e12952.CrossRefPubMed Eid, R.A., et al. 2019. A high-fat diet rich in corn oil induces cardiac fibrosis in rats by activating JAK2/STAT3 and subsequent activation of ANG II/TGF-1beta/Smad3 pathway: The role of ROS and IL-6 trans-signaling. Journal of Food Biochemistry 43 (8): e12952.CrossRefPubMed
18.
Zurück zum Zitat Li, T., et al. 2022. Circular RNA Plasmacytoma Variant Translocation 1 (CircPVT1) knockdown ameliorates hypoxia-induced bladder fibrosis by regulating the miR-203/Suppressor of Cytokine Signaling 3 (SOCS3) signaling axis. Bioengineered 13 (1): 1288–1303.CrossRefPubMedPubMedCentral Li, T., et al. 2022. Circular RNA Plasmacytoma Variant Translocation 1 (CircPVT1) knockdown ameliorates hypoxia-induced bladder fibrosis by regulating the miR-203/Suppressor of Cytokine Signaling 3 (SOCS3) signaling axis. Bioengineered 13 (1): 1288–1303.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Wu, S.W., et al. 2021. Obesity attenuates ventilator-induced lung injury by modulating the STAT3-SOCS3 pathway. Frontiers in Immunology 12: 720844. Wu, S.W., et al. 2021. Obesity attenuates ventilator-induced lung injury by modulating the STAT3-SOCS3 pathway. Frontiers in Immunology 12: 720844.
20.
Zurück zum Zitat Li, X., et al. 2022. Effect of SOCS3 on vocal fold fibroblast activation by regulating the JAK2/STAT3 signalling pathway. Tissue and Cell 79: 101965. Li, X., et al. 2022. Effect of SOCS3 on vocal fold fibroblast activation by regulating the JAK2/STAT3 signalling pathway. Tissue and Cell 79: 101965.
21.
Zurück zum Zitat Alshaer, W., et al. 2021. siRNA: Mechanism of action, challenges, and therapeutic approaches. European journal of pharmacology 905: 174178.CrossRefPubMed Alshaer, W., et al. 2021. siRNA: Mechanism of action, challenges, and therapeutic approaches. European journal of pharmacology 905: 174178.CrossRefPubMed
22.
Zurück zum Zitat Li, J., et al. 2018. Expression of tenascin-C in a rat vocal fold injury model and its regulation of fibroblasts. The Laryngoscope 128 (9): E316–E322.CrossRefPubMed Li, J., et al. 2018. Expression of tenascin-C in a rat vocal fold injury model and its regulation of fibroblasts. The Laryngoscope 128 (9): E316–E322.CrossRefPubMed
23.
Zurück zum Zitat Branski, R.C., et al. 2009. Effects of transforming growth factor-beta1 on human vocal fold fibroblasts. The Annals of Otology, Rhinology, and Laryngology 118 (3): 218–226.CrossRefPubMed Branski, R.C., et al. 2009. Effects of transforming growth factor-beta1 on human vocal fold fibroblasts. The Annals of Otology, Rhinology, and Laryngology 118 (3): 218–226.CrossRefPubMed
24.
25.
Zurück zum Zitat San Martin, S., et al. 2013. Stat3 and Socs3 expression patterns during murine placenta development. European Journal of Histochemistry 57 (2): e19.CrossRefPubMedPubMedCentral San Martin, S., et al. 2013. Stat3 and Socs3 expression patterns during murine placenta development. European Journal of Histochemistry 57 (2): e19.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Barclay, J.L., et al. 2009. SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL. International Journal of Cancer 124 (8): 1756–1766.CrossRefPubMed Barclay, J.L., et al. 2009. SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL. International Journal of Cancer 124 (8): 1756–1766.CrossRefPubMed
27.
Zurück zum Zitat Pascarella, S., et al. 2013. Intrahepatic mRNA levels of SOCS1 and SOCS3 are associated with cirrhosis but do not predict virological response to therapy in chronic hepatitis C. Liver International 33 (1): 94–103.CrossRefPubMed Pascarella, S., et al. 2013. Intrahepatic mRNA levels of SOCS1 and SOCS3 are associated with cirrhosis but do not predict virological response to therapy in chronic hepatitis C. Liver International 33 (1): 94–103.CrossRefPubMed
28.
Zurück zum Zitat Tang, L.Y., et al. 2017. Transforming Growth Factor-beta (TGF-beta) directly activates the JAK1-STAT3 axis to induce hepatic fibrosis in coordination with the SMAD pathway. Journal of Biological Chemistry 292 (10): 4302–4312. Tang, L.Y., et al. 2017. Transforming Growth Factor-beta (TGF-beta) directly activates the JAK1-STAT3 axis to induce hepatic fibrosis in coordination with the SMAD pathway. Journal of Biological Chemistry 292 (10): 4302–4312.
29.
Zurück zum Zitat Yang, Y.Z., et al. 2019. Magnesium isoglycyrrhizinate ameliorates high fructose-induced liver fibrosis in rat by increasing miR-375-3p to suppress JAK2/STAT3 pathway and TGF-beta1/Smad signaling. Acta Pharmacologica Sinica 40 (7): 879–894.CrossRefPubMed Yang, Y.Z., et al. 2019. Magnesium isoglycyrrhizinate ameliorates high fructose-induced liver fibrosis in rat by increasing miR-375-3p to suppress JAK2/STAT3 pathway and TGF-beta1/Smad signaling. Acta Pharmacologica Sinica 40 (7): 879–894.CrossRefPubMed
30.
Zurück zum Zitat Branski, R.C., et al. 2016. The role of Smad3 in the fibrotic phenotype in human vocal fold fibroblasts. The Laryngoscope 126 (5): 1151–1156.CrossRefPubMed Branski, R.C., et al. 2016. The role of Smad3 in the fibrotic phenotype in human vocal fold fibroblasts. The Laryngoscope 126 (5): 1151–1156.CrossRefPubMed
31.
Metadaten
Titel
SOCS3 Silencing Promotes Activation of Vocal Fold Fibroblasts via JAK2/STAT3 Signaling Pathway
verfasst von
Xueyan Li
Rong Hu
Haizhou Wang
Wen Xu
Publikationsdatum
08.05.2023
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 4/2023
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-023-01810-9

Weitere Artikel der Ausgabe 4/2023

Inflammation 4/2023 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.