Impaired Liver Regenerative Response following Administration of Anti-TLR4 Antibody in Mice

Marlini, Muhamad; Mabuchi, Ayako; Mallard, Beth; Hairulhisyam, Ngatiman M.; Akashi-Takamura, Sachiko; Miyata, Haruo; Harper, Jacquie L.; Wheatley, Antony M.

doi:10.1016/s0168-8278(16)00427-x

Cited by 1 publication

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent hepatocyte proliferation and liver mass restoration therefore proceeds normally following a normal cytokine response, as demonstrated in our current study. This is consistent with previous studies, where inhibition of LPS/TLR4 signaling leads to impaired liver regeneration [ 13 ]. It has been demonstrated that colonization of sterile gut with normal gut microbiota promotes physiological and structural functions of the intestinal barrier, which further contributes to the intestinal homeostasis [ 22 ].…”

Section: Discussionsupporting

confidence: 94%

“…Our findings indicating reduced liver regeneration in GF mice were in accordance with previous studies, where reduced liver regeneration was observed following PHx in mice with diminished LPS/TLR4 signaling. The reduced liver regeneration was demonstrated in GF, and antibiotic-treated mice [ 5 , 21 ], and in LPS-hyposensitive, C3H/HeJ mice [ 13 , 14 ]. Therefore, our findings reveal a further implication of an underdeveloped immune system of the sterile mouse, and the importance of gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

“…Stimulation of the remnant liver following PHx via administration of exogenous endotoxin promotes hepatocyte proliferation, while restriction of endotoxin via administration of antibiotic impairs liver regeneration [ 6 , 12 ]. Furthermore, acute blockade of LPS/TLR4 signaling using anti-TLR4 antibody (MTS510) impairs liver regenerative response in C3H/HeN mice [ 13 ]. Mice hyposensitive to LPS due to a tlr4 gene mutation demonstrate reduced liver regeneration following PHx [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, acute blockade of LPS/TLR4 signaling using anti-TLR4 antibody (MTS510) impairs liver regenerative response in C3H/HeN mice [ 13 ]. Mice hyposensitive to LPS due to a tlr4 gene mutation demonstrate reduced liver regeneration following PHx [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impact of Gut Recolonization on Liver Regeneration: Hepatic Matrisome Gene Expression after Partial Hepatectomy in Mice

Amin,

Hairulhisyam,

Aqilah

et al. 2023

IJMS

View full text Add to dashboard Cite

The hepatic matrisome is involved in the remodeling phase of liver regeneration. As the gut microbiota has been implicated in liver regeneration, we investigated its role in liver regeneration focusing on gene expression of the hepatic matrisome after partial hepatectomy (PHx) in germ-free (GF) mice, and in GF mice reconstituted with normal gut microbiota (XGF). Liver mass restoration, hepatocyte proliferation, and immune response were assessed following 70% PHx. Hepatic matrisome and collagen gene expression were also analyzed. Reduced liver weight/body weight ratio, mitotic count, and hepatocyte proliferative index at 72 h post PHx in GF mice were preceded by reduced expression of cytokine receptor genes Tnfrsf1a and Il6ra, and Hgf gene at 3 h post PHx. In XGF mice, these indices were significantly higher than in GF mice, and similar to that of control mice, indicating normal liver regeneration. Differentially expressed genes (DEGs) of the matrisome were lower in GF compared to XGF mice at both 3 h and 72 h post PHx. GF mice also demonstrated lower collagen expression, with significantly lower expression of Col1a1, Col1a2, Col5a1, and Col6a2 compared to WT mice at 72 h post PHx. In conclusion, enhanced liver regeneration and matrisome expression in XGF mice suggests that interaction of the gut microbiota and matrisome may play a significant role in the regulation of hepatic remodeling during the regenerative process.

show abstract

Section: Discussionsupporting

confidence: 94%