Podocytes are actin-rich epithelial cells whose effacement and detachment are the main cause of glomerular disease. Crk family proteins: Crk1/2 and CrkL are reported to be important intracellular signaling proteins that are involved in many biological processes. However, the roles of them in maintaining podocyte morphology and function remain poorly understood. In this study, specific knocking down of Crk1/2 and CrkL in podocytes caused abnormal cell morphology, actin cytoskeleton rearrangement and dysfunction in cell adhesion, spreading, migration, and viability. The p130Cas, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, p38 and JNK signaling pathways involved in these alterations. Furthermore, knocking down CrkL alone conferred a more modest phenotype than did the Crk1/2 knockdown and the double knockdown. Kidney biopsy specimens from patients with focal segmental glomerulosclerosis and minimal change nephropathy showed downregulation of Crk1/2 and CrkL in glomeruli. In zebrafish embryos, Crk1/2 and CrkL knockdown compromised the morphology and caused abnormal glomerular development. Thus, our results suggest that Crk1/2 and CrkL expression are important in podocytes; loss of either will cause podocyte dysfunction, leading to foot process effacement and podocyte detachment.

Non-coding RNAs (ncRNAs) are often reviewed as lists of molecules associated with individual cardiovascular phenotypes. Here, we instead ask how ncRNAs alter the probability, timing, and stability of cardiovascular cell-state transitions across development, injury, and disease. We organize evidence for microRNAs, long non-coding RNAs, circular RNAs, and extracellular-vesicle-associated RNAs around four regulatory operations: chromatin and transcriptional competence, post-transcriptional tuning, multicellular communication, and persistence or reversibility of the response. Cardiac development provides the reference trajectory from mesoderm specification through progenitor commitment, morphogenesis, and functional maturation. Regeneration is evaluated separately from DNA synthesis or cardioprotection and requires daughter-cardiomyocyte formation, maturation, electrical integration, scar replacement, and durable functional recovery. The disease section uses a bounded cardiovascular scope: atherosclerosis and hypertension are included as determinants of coronary supply and ventricular load, whereas renal and pulmonary examples are restricted to mechanisms that directly affect cardiac afterload or ventricular adaptation. Across these settings, the most recurrent ncRNAs are not universal switches; their effects depend on cell identity, subcellular localization, endogenous abundance, dose, and disease phase. We therefore grade mechanistic claims by target engagement, cell and species specificity, physiological stoichiometry, in vivo rescue, and human validation. This framework converts a molecule-by-molecule catalogue into a critical account of when ncRNAs are causal regulators, context-dependent modifiers, or biomarkers of changing tissue composition.