Extended Data Fig. 9. nmrHAS2 reduces pro-inflammatory response in vivo and protects cells from oxidative stress.

a. nmrHAS2 mice produce significantly lower plasma TNFα levels 4 h and 24 h after LPS challenge in 5-months old female mice (n=4).

b. nmrHAS2 mice produce significantly lower plasma IL6 levels 4 h after LPS challenge in 5- months old female mice (n=4).

c. nmrHAS2 mice show lower IL1β and TNFα levels in liver 24 h post LPS challenge in 5-months old female mice (n=4).

d. nmrHAS2 mice show lower IL1β and TNFα levels in the spleen 24 h post LPS challenge in 5- months old female mice (n=4).

e. nmrHAS2 mice show lower IL1β and TNFα levels in kidney 24 h post LPS challenge in 5- months old female mice (n=4).

f. Pulse field gel shows nmrHAS2 skin fibroblasts produce more hyaluronic acid. compared to CreER fibroblasts. HAase treated samples were run in parallel to confirm the specificity of HA staining. Media from three different cell lines was pooled for HA extraction. Experiments were repeated for three times and showed a similar result.

g. Levels of relative on gel HA intensity. The intensity of HA was quantified using ImageJ. Intensity of nmrHAS2 group was normalized to the CreER group.

h. Skin fibroblasts isolated from nmrHAS2 mice are more resistant to H₂O₂ treatment. Fibroblasts were isolated from 5-months old female mice (n=4). p-values were calculated using unpaired two-tailed t-test.

a-e. p values were calculated by two-tailed unpaired t-test. Bars represent the means, error bars show the standard errors, dots represent biological replicates.