TABLE 7.

Summary of selected studies highlighting the role of EGFR signalling in renal fibrosis.

Number	Model	Methodology	Findings/Results/Conclusion relevant to EGFR	Study Reference
1	Mouse models and Human CKD patients	Unilateral ureteral obstruction induced renal fibrosis in T1D and T2D nephropathies	Significant increase in HER2	Li, H et al. (2019)
2	Mice model	Erlotinib action on CKD rats with remnant kidney	Inhibiting Akt and ERK 1/2 signaling resulted in reduced levels of cortical profibrogenic genes along with glomerulosclerosis and tubulointerstitial damage	Yamamoto et al. (2018)
3	Murine model	EGFR mimotope in unilateral ureteral obstruction	Improved renal fibrosis, decreased expression of collagen I, fibronectin and α-SMA	Yang et al. (2019)
4	Mice model	Ang II-stimulated mice treated with EGFR inhibitor 453	Inhibition of AKT and ERK pathways 453 also inhibited the activation of fibrotic pathways such as collagen, CFGF, TGF-β	Skibba et al. (2016)
5	Mice model	Usage of short hairpin RNA knockdown to inhibit the activation of EGFR in Angiotensin II-treated SV40 mesangial cells	Abolished buildup of fibrotic markers including CTGF and collagen IV	Qian et al. (2016)
6	Mice model	PAR2 activation in kidney tubular epithelial cells	Enhancement of Smad2 activation and release of pro-fibrotic factors via transactivation of EGF and TGFβ	Chung et al. (2013)
7	Murine model	Erlotinib treated aldosterone-mediated tissue fibrosis mice	TGF-β, α-SMA, and mesangial matrix proteins including collagen Ⅳ and fibronectin had inhibited expression	Sheng et al. (2016)
8	Mouse model	EGFR activation by expressing EGFR ligand hHB-EGF	Evolvement of progressive renal tubulointerstitial fibrosis	Overstreet et al. (2017)
9	Human HK-2 cell line	Incrementing concentrations of albumin on fibrosis indicators and mediators in models with and without γ-secretase inhibitor	EGFR has a major role in albumin-induced fibrotic events via halting γ-secretase activity	Slattery et al. (2013)
10	Murine model	PP1 treating cultured renal interstitial fibroblasts	Src inhibition prevented activation of signaling pathways including TGF- β1, EGFR and STAT3, ameliorating renal fibrosis	Yan et al. (2016)
11	Mice model	Unilateral ureteral obstruction resulting in renal fibrosis	Decreased renal fibrosis was found in Fyn-deficient mice, by inhibition of phosphor-STAT3	Seo et al. (2016)
12	Murine model	Administration of CCN2 with EGFR blockade	Decreased fibrotic response in kidney	Rayego-Mateos et al. (2018a)
13	Mice model	Ang II with endothelial HB-EGF deletion	Compared with controls, decreased EGFR activation and diminished renal fibrosis	Zeng et al. (2016)
14	Mouse model	Using a Smad3-dependent mechanism, Erbb4-IR induced by TGF-β1 was silenced	Reduced renal fibrosis along with blockage of collagen I and α-SMA expressions that are TGF-β1-induced in vitro	Feng et al. (2018)
15	Mouse model	Silencing Erbb4-IR induced by T2DN	Protecting the kidney in db/db mice models from progressive renal injury due to amplified miR-29b	Sun et al. (2018)
16	Mice model	Tempol-treated CKD mice	TGF-ß/Smad3-induced renal fibrosis along with EGFR/MAPK pathways activation was inhibited	Ding et al. (2015)
17	Mice model	ADAM17 lacking Ang II-infused mice	In vivo transient protective effects from renal fibrosis	Shen et al. (2017)
18	Murine model	HDAC 1 blockage in unilateral ureteral obstruction mice	Modulation of TGF-beta and EGFR signaling resulted in amelioration of renal fibrosis and inhibition of the activation of renal fibroblasts	Liu et al. (2013)
19	Mouse model	HDAC 3 blockage in renal interstitial fibrosis model of obstructive nephropathy	Attenuation of renal interstitial fibrosis	Ponnusamy et al. (2014)
20	C57BL/6J mice	Expressing of EGFR along with HUWE1 in a UUO mice model	HUWE1 regulated EGFR expression and resulted in a protective effect against kidney injury	Zhu, Q et al. (2020)
21	C57BL/6 mice	Renal fibrosis generated by a UUO and adenine diet (AD) investigating SAMiRNA-AREG effect on the disease	SAMiRNA-AREG suppressed EGFR signals and is considered as a new siRNA treatment for renal fibrosis	Son et al. (2021)