Figure 5 from Transforming Growth Factor-β1 (TGFβ1) Stimulates Connective Tissue Growth Factor (CCN2/CTGF) Expression in Human Gingival Fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent Mechanism | Semantic Scholar (2024)

A novel pathway in gingival fibroblasts in which inhibition of GSK-3β attenuates CCN2/CTGF expression is identified, consistent with previous studies performed in other cell models.

Real-time RT-PCR and Western blot analysis indicate that CTGF is critical to the fibrosis process in wounded human cornea, acting via upregulation and activation of JNK signaling pathway.

Curcumin significantly abrogated the TGFβ1-induced CCN2 in HGFs by inhibiting the phosphorylations of Src, JNK, and Smad3, and curcumin potentially qualifies as a useful agent for the control of GO.

While both Rac1 and RhoA are rapidly activated in response to TGF-beta1 in human mesangial cells, only Rac1 activation enhances events that contribute to mesangia cell collagen expression, through a positive feedback loop involving PI3K.

The results of this study suggest that thrombin-induced CCN2 expression may occur through PAR1, reactive oxygen species, ASK1, and JNK signaling in HGFs and curcumin could effectively inhibit CCN 2 expression through JNK suppression.

The results indicated that NOX4-derived ROS play pivotal roles in activating Src kinase activity leading to the activation of canonical (Smad3) and noncanonical (JNK) cascades that cooperate to attain maximum CCN2 expression.

Evidence is provided for a dual effect of HGF on CTGF regulation in human tubular epithelial cells: transient upregulation of CTGF in the absence of TGF-beta, which was related to alterations of cell morphology, and interference with T GF-beta-mediated CTGF induction after prolonged incubation.

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Two mechanisms by which TGFβ1-stimulated CCN2/CTGF levels in human gingival fibroblasts resist down-regulation by PGE2 are identified: (i) cAMP cross-talk with MAPK pathways is limited in gingiver fibro Blasts; (ii) P GE2 activation of the EP3 prostanoid receptor stimulates the activation of JNK.

The hypothesis that CTGF/CCN2 is expressed in human gingival fibromatosis tissues and contributes to this form of non‐drug‐induced gingiver overgrowth is investigated, suggesting that interactions between epithelial and connective tissues could contribute to gingivals fibrosis.

KO and WT animals demonstrated a similar inflammatory response to overexpression of IL-1β indicating that inflammation must link to the Smad3 pathway, likely through TGF-β, to induce progressive fibrosis.

The data suggest that Simvastatin can modify critical determinants of the profibrogenic machinery responsible for the aggressive clinical profile of IPF, and potentially prevents adverse lung parenchymal remodeling associated with persistent myofibroblast formation.

An abundance of connective tissue growth factor (CTGF/CCN2) in human platelets was discovered, which was released along with the coagulation process, and may be now regarded as one of the major functional components of platelets.

A first-generation small-molecule inhibitor of Rac GTPase targeting Rac activation by GEF, identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification, is reported.

The constitutive overexpression of CTGF in SSc fibroblasts seems to be independent of TGFβ signaling but dependent at least in part on Sp1, suggesting that phosphorylation of Sp1 normally reduces Sp1 binding to DNA.

The broad role played by the CCN family in basic and clinical endocrinology is illustrated and the relationship between CCN proteins and hormone action, skeletal growth, placental angiogenesis, IGF-binding proteins and diabetes-induced fibrosis is highlighted.

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