Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of myofibroblast differentiation. [GO_REF:0000058, GOC:BHF, GOC:BHF_miRNA, GOC:rph, GOC:TermGenie, PMID:20533548]
Negative regulation of myofibroblast differentiation is a complex biological process that involves a multifaceted interplay of signaling pathways, transcription factors, and extracellular matrix interactions. Myofibroblasts are specialized fibroblasts that exhibit contractile properties and play crucial roles in wound healing, tissue repair, and fibrosis. The differentiation of fibroblasts into myofibroblasts is tightly regulated, and its dysregulation can contribute to pathological conditions such as fibrosis. The negative regulation of myofibroblast differentiation involves a range of mechanisms aimed at suppressing the expression of myofibroblast-specific markers, inhibiting their activation and proliferation, and promoting their apoptosis. One key mechanism involves the inhibition of transforming growth factor-beta (TGF-beta) signaling. TGF-beta is a potent inducer of myofibroblast differentiation, and its signaling pathway is frequently dysregulated in fibrotic diseases. Negative regulators of TGF-beta signaling, such as SMAD7 and Smad-interacting protein 1 (SIP1), can suppress TGF-beta-induced myofibroblast differentiation. Another important pathway involves the regulation of microRNAs (miRNAs). Certain miRNAs, such as miR-29, have been shown to inhibit myofibroblast differentiation by targeting key downstream effectors of TGF-beta signaling. Additionally, miRNAs can also regulate the expression of other genes involved in myofibroblast differentiation, including those involved in cell cycle control and apoptosis. The extracellular matrix (ECM) also plays a crucial role in regulating myofibroblast differentiation. ECM components, such as fibronectin and collagen, can influence myofibroblast activation and proliferation through interactions with cell surface receptors. Furthermore, various signaling pathways, including Wnt, Notch, and Hippo, have been implicated in the negative regulation of myofibroblast differentiation. These pathways can modulate the expression of key transcription factors and signaling molecules involved in myofibroblast differentiation. In summary, negative regulation of myofibroblast differentiation involves a complex interplay of multiple cellular and molecular mechanisms. Understanding these mechanisms is crucial for developing therapeutic strategies targeting fibrotic diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Programmed cell death protein 4 | A programmed cell death protein 4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q53EL6] | Homo sapiens (human) |
| Retinoblastoma-associated protein | A retinoblastoma-associated protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06400] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tubercidin | tubercidin : An N-glycosylpyrrolopyrimidine that is adenosine in which the in the 5-membered ring that is not attached to the ribose moiety is replaced by a carbon. Tubercidin is produced in the culture broth of Streptomyces tubericidus. Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids. | antibiotic antifungal agent; N-glycosylpyrrolopyrimidine; ribonucleoside | antimetabolite; antineoplastic agent; bacterial metabolite |
| staurosporine | indolocarbazole alkaloid; organic heterooctacyclic compound | apoptosis inducer; bacterial metabolite; EC 2.7.11.13 (protein kinase C) inhibitor; geroprotector | |
| sirolimus | sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent. Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. | antibiotic antifungal drug; cyclic acetal; cyclic ketone; ether; macrolide lactam; organic heterotricyclic compound; secondary alcohol | antibacterial drug; anticoronaviral agent; antineoplastic agent; bacterial metabolite; geroprotector; immunosuppressive agent; mTOR inhibitor |