Drugs targeting CTGF in the treatment of pulmonary fibrosis.

Pulmonary fibrosis represents the final alteration seen in a wide variety of lung disorders characterized by increased fibroblast activity and the accumulation of substantial amounts of extracellular matrix, along with inflammatory damage and the breakdown of tissue architecture. This condition is marked by a significant mortality rate and a lack of effective treatments. The depositing of an excessive quantity of extracellular matrix protein follows the damage to lung capillaries and alveolar epithelial cells, leading to pulmonary fibrosis and irreversible damage to lung function. It has been proposed that the connective tissue growth factor (CTGF) plays a critical role in the advancement of pulmonary fibrosis by enhancing the accumulation of the extracellular matrix and exacerbating fibrosis. In this context, the significance of CTGF in pulmonary fibrosis is examined, and a summary of the development of drugs targeting CTGF for the treatment of pulmonary fibrosis is provided.

The role of molecular chaperone CCT/TRiC in translation elongation: A literature review.

Protein synthesis from mRNA is an energy-intensive and strictly controlled biological process. Translation elongation is a well-coordinated and multifactorial step in translation that ensures the accurate and efficient addition of amino acids to a growing nascent-peptide chain encoded in the sequence of messenger RNA (mRNA). Which undergoes dynamic regulation due to cellular state and environmental determinants. An expanding body of research points to translational elongation as a crucial process that controls the translation of an mRNA through multiple feedback mechanisms. Molecular chaperones are key players in protein homeostasis to keep the balance between protein synthesis, folding, assembly, and degradation. Chaperonin-containing tailless complex polypeptide 1 (CCT) or tailless complex polypeptide 1 ring complex (TRiC) is an essential eukaryotic molecular chaperone that plays an essential role in assisting cellular protein folding and suppressing protein aggregation. In this review, we give an overview of the factors that influence translation elongation, focusing on different functions of molecular chaperones in translation elongation, including how they affect translation rates and post-translational modifications. We also provide an understanding of the mechanisms by which the molecular chaperone CCT plays multiple roles in the elongation phase of eukaryotic protein synthesis.

Muscle satellite cells are impaired in type 2 diabetic mice by elevated extracellular adenosine.

Muscle regeneration is known to be defective under diabetic conditions. However, the underlying mechanisms remain less clear. Adult quiescent muscle satellite cells (MuSCs) from leptin-receptor-deficient (i.e., db/db) diabetic mice are defective in early activation in vivo, but not in culture, suggesting the involvement of pathogenic niche factors. Elevated extracellular adenosine (eAdo) and AMP (eAMP) are detected under diabetic conditions. eAdo and eAMP potently inhibit cell cycle re-entry of quiescent MuSCs and injury-induced muscle regeneration. Mechanistically, eAdo and eAMP engage the equilibrative Ado transporters (ENTs)-Ado kinase (ADK)-AMPK signaling axis in MuSCs to inhibit the mTORC1-dependent cell growth checkpoint. eAdo and eAMP also inhibit early activation of quiescent fibroadipogenic progenitors and human MuSCs by the same mechanism. Treatment of db/db diabetic mice with an ADK inhibitor partially rescues the activation defects of MuSCs in vivo. Thus, both ADK and ENTs represent potential therapeutic targets for restoring the regenerative functions of tissue stem cells in patients with diabetes.