In DKD, hyperglycemia aberrantly activates L-type VGCCs (e.g., Cav1.2) in mesangial cells, increasing calcium current density (2–3 fold) and driving fibrosis via: (1) inflammatory cytokine release: Calcium signaling activates nuclear factor of activated T cells (NFAT), promoting TGF-β1, connective tissue growth factor (CTGF), and IL-6 synthesis; (2) extracellular matrix (ECM) deposition: Upregulating collagen IV and fibronectin expression; (3) cellular proliferation: Activating ERK1/2 pathways to induce pathological mesangial cell hyperplasia (108). Here, TGFB1 is linked to Hyperglycemia.