Written by Li Hui, He Bingqiang

Editor in charge ︱ Wang Sizhen

Editor︱Yang Binwei

The main function of D-dopachrome tautomerase (D-DT) is to catalyze the formation of 5,6-dihydroxyindole from D-dopachrome [1]

On August 14, 2022, the research group of Professor Wang Yongjun of Nantong University published a study entitled "D-dopachrome tautomerase drives astroglial inflammation via NF-κB signaling following spinal cord injury" in Cell & Bioscience This paper expounds the regulatory mechanism of D-DT as a pro-inflammatory factor mediating the inflammatory response of spinal cord astrocytes

First, by constructing a rat model of spinal cord impingement injury, the authors examined the expression changes of D-DT at 0d, 1d, 4d and 7d after spinal cord injury (SCI), and found that D-DT expression was significantly up-regulated after SCI

Figure 1 Induced expression of D-DT in astrocytes at the injury site after spinal cord injury in rats

(Image source: Li et al.

Subsequently, the authors used D-DT recombinant protein to stimulate rat primary astrocytes.

Figure 2 NF-κB is a key regulator of D-DT-stimulated astrocyte responses

(Image source: Li et al.

To further validate the sequencing results, the authors cultured primary astrocytes and studied the functional receptors through which D-DT acts

Finally, the authors examined the effect of D-DT selective inhibitor 4-CPPC on the inflammatory response of injured spinal cord and the recovery of motor function in rats by intrathecal administration at the spinal cord injury
.

The results showed that 4-CPPC significantly decreased the expression of p65NF-κB and inflammatory factors in astrocytes (Fig.
3i–m)
.

Morphological observation found that 4-CPPC could significantly control the secondary spinal cord injury triggered by the inflammatory response (Fig.
3n,o)
.

Behavioral tests showed that inhibiting the activity of D-DT in the injured spinal cord could effectively improve the hindlimb motor function of rats (Fig.
3p)
.

In conclusion, inhibiting the activity of D-DT after spinal cord injury can inhibit astrocyte-mediated inflammatory response and improve motor function in rats
.

Figure 3 D-DT inhibitor effectively attenuates NF-κB signaling and improves motor function after spinal cord injury in rats

(Image source: Li et al.
, Cell & Bioscience, 2022)

Original link: https://doi.
org/10.
1186/s13578-022-00867-7

This research was supported by the National Natural Science Foundation of China (No.
3187211) and the China Postdoctoral Science Foundation (No.
2020M681689)
.

First author: Li Hui (first from left), He Bingqiang (second from left); Corresponding author: Professor Wang Yongjun (first from right)

(Photo provided by: Key Laboratory of Nerve Regeneration, Nantong University)

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