
-   C/EBPdelta regulates cell cycle and self-renewal of human limbal stem cells. Forced expression of C/EBPdelta inhibits the growth of limbal colonies and increases the cell cycle length of primary limbal cells through the activity of p27(Kip1) and p57(Kip2) [PMID: 17562792]. Activated Stat3 proceeds to C/EBPdelta then to myostatin and causes muscle wasting. p-Stat3 initiates muscle wasting via C/EBPdelta, stimulating myostatin, a negative muscle growth regulator [PMID: 24011072].
-   The CCAAT/enhancer binding protein delta (CEBPD, C/EBPdelta, NF-IL6beta) is induced in many inflammation-related diseases including early stages of Alzheimer's disease (AD). CEBPD is upregulated in the astrocytes of AD patients. Astrocytic CEBPD plays a role in regulating inflammatory marker pentraxin-3 (PTX3) and attenuating macrophage-mediated phagocytosis of damaged neuron cells, demonstrated a role for CEBPD in the accumulation of damaged neurons, which is a hallmark of AD pathogenesis [PMID: 21112127].
-   Inflammation and hypoxia are known to promote the metastatic progression of tumors. C/EBPdelta is induced by hypoxia in tumors in vivo. C/EBPdelta directly inhibits expression of the tumor suppressor FBXW7, encoding an F-box protein that promotes degradation of mTOR. Consequently, C/EBPdelta enhances mTOR/AKT/S6K1 signaling and augments translation and activity of hypoxia-inducible factor-1alpha (HIF-1alpha), which is necessary for hypoxia adaptation and metastasis [PMID: 21076392].
-   In human epidermoid carcinoma, human NF-IL6beta was an immediate-early gene activated by epidermal growth factor (EGF) stimulation. CREB was involved in regulating the NF-IL6beta gene transcriptional activity mediated by p38 MAPK [PMID: 15901830].
-   Starvation was identified as a stimulus that triggers the FOXO-C/EBPdelta signaling pathway. FOXO1 was found to enhance the promoter activity of target genes in cooperation with C/EBPdelta and ATF4 to regulate skeletal muscle atrophy transcriptional program during fasting [PMID: 35061305].

## Summary

C/EBPdelta, encoded by the Cebpd gene, is a transcription factor that's upregulated in response to various stressors and inflammatory signals, as indicated by its increased expression during conditions like chronic kidney disease (CKD), muscle atrophy, and starvation [CS: 7]. In the context of skeletal muscle, this upregulation seems to be a response mechanism to counteract muscle wasting and damage [CS: 6]. For instance, the activation of C/EBPdelta in CKD, as shown by increased expression in muscles of CKD patients, can be linked to its role in initiating muscle wasting via stimulating myostatin, a negative regulator of muscle growth [CS: 5]. This suggests that in a diseased or stressed state, C/EBPdelta acts to limit muscle growth, possibly as a way to conserve energy or resources under unfavorable conditions [CS: 6].

Similarly, during starvation, the increase in C/EBPdelta expression is associated with the induction of the ubiquitin-proteasome system, leading to muscle atrophy [CS: 7]. This mechanism might function as a biological response to energy deficiency, where muscle protein degradation provides amino acids for energy production or for maintaining essential physiological functions [CS: 8]. In essence, the dysregulation of Cebpd in skeletal muscle diseases and toxicities appears to be a stress response mechanism, where its activation under such conditions leads to a decrease in muscle mass and function, ostensibly as a means to adapt to energy scarcity or to mitigate further damage in diseased states [CS: 6].
