Fig. 1.

Origination and activation of myofibroblasts. In tubulointerstitium, injury results in epithelial dedifferentiation, which is characterized by the upregulation of Notch, Wnt, Hedgehog (Hh), and SOX9 pathways. Persistent damage leads to cycle arrest and senescence of tubular epithelial cells, accompanying the secretion of profibrotic factors and senescence-associated secretory phenotype (SASP). Injured VCAM-1⁺ tubules secrete paracrine mediators such as TGF-β, Hh, and Wnt ligands, which impact interstitial pericytes and fibroblasts to activate myofibroblast differentiation, proliferation, and ECM accumulation. Of note, the different population of immune cell including macrophage, lymphocyte, neutrophil, and basophil also have been found in the interstitial space. And these cells expressing specific markers play an important part in kidney fibrosis