Format

Send to

Choose Destination
Endocrine. 2019 Mar 4. doi: 10.1007/s12020-019-01880-6. [Epub ahead of print]

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy.

Author information

1
Department of Anesthesiology, Second Affiliated Hospital of Wenzhou Medical University, Pain Medicine Institute of Wenzhou Medical University, 325035, Zhejiang, China.
2
Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, 07103, USA.
3
Department of Anesthesiology, Second Affiliated Hospital of Wenzhou Medical University, Pain Medicine Institute of Wenzhou Medical University, 325035, Zhejiang, China. lijun0068@163.com.
4
Department of Anesthesiology, Second Affiliated Hospital of Wenzhou Medical University, Pain Medicine Institute of Wenzhou Medical University, 325035, Zhejiang, China. caohong1955@21cn.com.

Abstract

PURPOSE:

The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy.

METHODS:

In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors (n= 8), while western blot (n= 5) and an immunofluorescence double staining experiment (n= 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons.

RESULTS:

The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro.

CONCLUSIONS:

Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.

KEYWORDS:

CAV-1; JAK2/STAT3; NR2B; Painful diabetic neuropathy

PMID:
30830585
DOI:
10.1007/s12020-019-01880-6

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center