Effect of JNK expression in dorsal root ganglia on histological change of foot skin in diabetic rats

AIM: To observe the change of skin histology in diabetic rats and to investigate the possible me-chanism of c-Jun N-terminal kinase (JNK) protein in the dorsal root ganglion (DRG) during the process. METHODS: Diabetic animal model was established in the male SD rats by intraperitoneal injection of streptozotocin. Plantar skin specimens of the rats were collected from control group, DM 2-week group (DM2), DM 4-week group (DM4), and DM 8-week group (DM8). Immunohistochemical staining and HE staining were used to observe the change of PGP 9.5 immunoreactive nerve terminals and the structures of the skin tissues. The protein expression of PGP 9.5 in the plantar skin tissues, and JNK and p-JNK protein in the DRG within lumbar 5, 6 (L5, 6), and sacral 1 (S1) spinal cord segments were detected by Western blotting. RESULTS: PGP 9.5 immunoreactive nerve terminals of the plantar skin of the rats mainly distributed in the basal layer of the epidermis and papillary dermis. Compared with control group, PGP 9.5 positive nerve terminals in DM4 group showed reduced density and sparse distribution. PGP 9.5 positive nerve terminals in DM8 group showed significantly reduced distribution, thinner nerve diameter, shorter length and distorted shape. Histological changes of the thinner epidermal tissue, reduced epidermal cell layers, uneven cell distribution and arrangement in DM4 group, and significantly reduced epidermal cell layers, swollen and blurred cells, increasing cell gap, lack of stratified epidermis arrangement for part of epidermis, atropal and degenerated dermal collagen fiber, significantly decreased subcutaneous fat in DM8 group were observed. The results of Western blotting showed that the protein expression of PGP 9.5 in the plantar skin tissue of DM rats was progressively decreased along with the disease, while the protein level of p-JNK in L5, 6-DRG or S1-DRG showed a gradual increasing trend. PGP 9.5 immunoreactive positive nerve terminal density of plantar skin in DM rats had a negative correlation with the protein level of p-JNK in L5, 6-DRG and S1-DRG (P<0.01), but showed a significant positive correlation with the plantar skin thickness (P<0.01). CONCLUSION: The protein level of p-JNK within L5, 6-DRG or S1-DRG in DM rats shows a progressive enhancement. At the same time, there is a significant change in the skin tissue density and structure. The changes of skin tissue and nerve morphology in DM rat may be related to the activation of JNK/SAPK pathway in L5, 6-DRG or S1-DRG cells. Blocking or inhibiting JNK/SAPK pathway may delay the diabetic peripheral neuropathy and reduce the risk of skin lesions.