Table 1:

Modes and characteristic features of intercellular communication in kidney fibrosis.

Modes of cell–cell communication	Mediators	Characteristic features	Routes	Relationship between sending and receiving cells	Mechanisms of action
Cell contact mediated	Specialized apparatus such as gap junction	Non-diffusional, only between neighboring cells	Physical contact	Neighboring cells: one-to-one	Biomolecules can directly pass from one cell to its neighboring cell without going through extracellular space
Soluble factors mediated	Growth factors, cytokines, chemokines	Diffusional, gradient dependent	Autocrine, paracrine, endocrine, juxtacrine	Ligand/receptor pair: one-to-one	Ligand secreted by sending cell binds to the specific receptor on the plasma membrane of receiving cell; this triggers a cascade of intracellular signaling, leading to the expression of target genes
EV mediated	EV-encapsulated proteins, miRNA, lncRNA mRNA, lipids	Diffusional, gradient dependent	Autocrine, paracrine, endocrine	One-to-many or many-to-many	EVs produced by sending cells can be taken up by receiving cells through direct fusion, endocytosis or receptor-mediated process; EVs elicit their actions by releasing the contents of the cargo
Extracellular niche mediated	Insoluble matricellular proteins	Non-diffusional, within spatially confined location	Autocrine, paracrine	One-to-many or many-to-many	Matricellular proteins secreted by producing cells are incorporated into the ECM network, orchestrating the formation of special niche; this regulates the activity and fate of receiving cells in the vicinity through binding to membrane receptors, recruiting and presenting soluble factors