Transforming growth factor-β (TGF-β) is an anti-inflammatory cytokine and is 
expressed in the injured spinal cord. TGF-β signals through receptors to 
activate Smad proteins, which translocate into the nucleus. In the present 
study, we investigated the chronological alterations and cellular locations of 
the TGF-β/Smad signaling pathway following spinal cord injury (SCI) in mice. 
ELISA analysis showed that the concentration of interleukin-6 (IL-6) in injured 
spinal cords significantly increases immediately after SCI, while the 
concentration of TGF-β gradually increased after SCI, peaked at 2 days, and then 
gradually decreased. Immunohistochemical studies revealed that Smad3 was mainly 
expressed in neurons of the spinal cord. Phosphorylated Smad3 at the C-terminus 
(p-Smad3C) was stained within the motor neurons in the anterior horn, while 
phosphorylated Smad3 at the linker regions (p-Smad3L) was expressed in 
astrocytes within gray matter. These findings suggest that SCI induces gradual 
increases in TGF-β and induces different activation of p-Smad3C and p-Smad3L. 
Phosphorylated Smad3C might be involved in neuronal degeneration after SCI, and 
p-Smad3L may play a role in glial scar formation by astrocytes.