Systemic Overexpression of GDF5 in Adipocytes but Not Hepatocytes Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver in Mice

Yang, Yinxue; Zhang, Wenting; Wu, Xiaohui; Wu, Jing; Sun, Chengjun; Luo, Feihong; Zhou, Pei

doi:10.1155/2021/8894685

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…BMP14, also known as growth differentiating factor 5 (GDF5), has so far mostly been studied in the context of cartilage and bone formation and homeostasis [7]. To date, only one study analyzed BMP14 in the context of chronic liver disease and found that the systemic overexpression of BMP14 in adipose tissues reduced high-fat diet-induced fatty liver disease in mice [8]. In addition, only a few studies exist regarding BMP14 and cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer

Sommer

Thasler²,

Bosserhoff

et al. 2023

Livers

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The activation of hepatic stellate cells (HSCs) is the key event of hepatic fibrosis. Furthermore, activated HSCs also play an important role in the progression of hepatocellular cancer (HCC). Bone morphogenetic protein 14 (BMP14) is a member of the TGF-β/BMP superfamily. So far, most studies have analyzed BMP14 in the context of bone and cartilage formation and homeostasis. The aim of this study was to assess the expression and function of BMP14 in liver fibrosis and HCC. The BMP14 expression increased during the in vitro activation of primary human HSCs and also in mouse models of liver fibrosis. In human HCC, as well as non-tumorous liver tissues, there was a significant correlation between the expression of BMP14 and alpha-smooth-muscle actin (α-SMA), an established marker for HSC activation. RNAi-mediated BMP14 suppression in activated HSCs resulted in the reduced expression of the transcription factors inhibitor of differentiation 1 (ID1) and ID2, known targets of BMP signaling. Interestingly, α-SMA and collagen expression was also reduced in BMP14-depleted cells, while treatment with recombinant BMP14 induced ID1, ID2, α-SMA and collagen expression. In human HCC cell lines, treatment with recombinant BMP14 induced proliferation, migratory activity and colony formation. In summary, our data indicate activated HSCs as a major cellular source of enhanced BMP14 expression in fibrotic liver disease and HCC, and show that BMP14 exhibits pro-fibrogenic as well as pro-tumorigenic effects. Future analyses will reveal the potential of this soluble growth factor as a therapeutic target or prognostic marker for the progression of fibrosis and HCC in patients with chronic liver disease.

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Section: Introductionmentioning

confidence: 99%

Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer

Sommer

Thasler²,

Bosserhoff

et al. 2023

Livers

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A novel bioavailable curcumin-galactomannan complex modulates the genes responsible for the development of chronic diseases in mice: A RNA sequence analysis

et al. 2021

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Polymorphism rs143384 GDF5 reduces the risk of knee osteoarthritis development in obese individuals and increases the disease risk in non-obese population

Novakov,

Novakova,

Churnosova

et al. 2024

Arthroplasty

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Background We investigated the effect of obesity on the association of genome-wide associative studies (GWAS)-significant genes with the risk of knee osteoarthritis (KOA). Methods All study participants (n = 1,100) were divided into 2 groups in terms of body mass index (BMI): BMI ≥ 30 (255 KOA patients and 167 controls) and BMI < 30 (245 KOA and 433 controls). The eight GWAS-significant KOA single nucleotide polymorphisms (SNP) of six candidate genes, such as LYPLAL1 (rs2820436, rs2820443), SBNO1 (rs1060105, rs56116847), WWP2 (rs34195470), NFAT5 (rs6499244), TGFA (rs3771501), GDF5 (rs143384), were genotyped. Logistic regression analysis (gPLINK online program) was used for SNPs associations study with the risk of developing KOA into 2 groups (BMI ≥ 30 and BMI < 30) separately. The functional effects of KOA risk loci were evaluated using in silico bioinformatic analysis. Results Multidirectional relationships of the rs143384 GDF5 with KOA in BMI-different groups were found: This SNP was KOA protective locus among individuals with BMI ≥ 30 (OR 0.41 [95%CI 0.20–0.94] recessive model) and was disorder risk locus among individuals with BMI < 30 (OR 1.32 [95%CI 1.05–1.65] allele model, OR 1.44 [95%CI 1.10–1.86] additive model, OR 1.67 [95%CI 1.10–2.52] dominant model). Polymorphism rs143384 GDF5 manifested its regulatory effects in relation to nine genes (GDF5, CPNE1, EDEM2, ERGIC3, GDF5OS, PROCR, RBM39, RPL36P4, UQCC1) in adipose tissue, which were involved in the regulation of pathways of apoptosis of striated muscle cells. Conclusions In summary, the effect of obesity on the association of the rs143384 GDF5 with KOA was shown: the “protective” value of this polymorphism in the BMI ≥ 30 group and the “risk” meaning in BMI < 30 cohort.

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Systemic Overexpression of GDF5 in Adipocytes but Not Hepatocytes Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver in Mice

Cited by 3 publications

References 23 publications

Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer

Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer

A novel bioavailable curcumin-galactomannan complex modulates the genes responsible for the development of chronic diseases in mice: A RNA sequence analysis

Polymorphism rs143384 GDF5 reduces the risk of knee osteoarthritis development in obese individuals and increases the disease risk in non-obese population

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