Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT/TMEM175 pathway.

BACKGROUND AND PURPOSE: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. METHODS: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-ß1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1ß in combination with TGF-ß1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. RESULTS: Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-ß1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. CONCLUSION: In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD.

[An observation on the micro-structure and form of annulus fibrosus of lumbar interverbral disc 4, 5].

We observed the structure and form of adult annulus fibrosus of lumbar intervertebral disc at the fibrous layer level. The annulus fibrosus of lumbar interverbral disc was delaminated by using microsurgical technique. 8 testing points were taken in each layer and the angles between their fibers going and horizontal plane were measured. The results showed that the fiber going angle at each measurement point continually increased with the increase of fibrous layer from outside to inside along the radial direction in horizontal plane. The least fiber going angle was 25 degrees - 30 degrees. The fiber going angle at the same layer gradually increased from front to back. The fiber going angle was 70 degrees - 90 degrees at the middle of the back of annulus fibrosus of lumbar interverbral disc. The fiber going was consistent with the posterior longitudinal ligament going. Through the normalized equation and normalized line, the fiber going angle at any point in any layer could be obtained conveniently. We also observed that the annuli fibrosus were interlaced in the front, left and right of annulus fibrosus of lumbar intervertebral disc. And there were more interlaced areas in local sides of lumbar intervertebral disc, but there was no interlaced areas between layers near the middle of posterior annulus fibrosus. So we came to the conclusion: Annulus fibrosus of lumbar intervertebral disc has a special micro-structure in adaptation with its function.