Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: The FGFR1/YAP1 axis is upregulated in human renal fibrosis, with single-cell transcriptomic validation and enrichment of Hippo pathway signaling in DKD. (A) Immunofluorescence micrographs showing co-localization of FGFR1 (red) and VE-cadherin (green) in adjacent non-cancerous (Normal) and renal fibrosis tissues. Bar = 50 μm and 10 μm. Dashed circles outline the glomeruli. (B) Immunofluorescence staining comparing co-localization of YAP1 (red) and VE-cadherin (green) between Normal and renal fibrosis tissues. Bar = 50 μm and 10 μm. Dashed circles outline the glomeruli. (C) Semi-quantitative immunofluorescence analysis of FGFR1 (left) and YAP1 (right) expression in renal endothelial cells. Both FGFR1 and YAP1 are significantly upregulated in renal fibrosis compared to Normal tissues (normalized to 1 arbitrary unit). n = 5. (D) UMAP shows cell population in kidneys from healthy controls and patients with DKD. PC principal cell of collecting duct, PT proximal tubule,TAL thick ascending limb of LoH, IC-a type A intercalated cell of collecting duct, CNT connecting tubule, PT-vc proximal tubule vascular loop cell, Endo endothelial cell, podo podocyte, IC-b type B intercalated cell of collecting duct, Vsmc vascular smooth muscle cell, Fib fibroblast. Data from: GSE131882 . (E) GSEA shows that the Hippo signaling pathway was enriched in the DKD group versus the control group (FDR = 0.039). (F) Graphic presentation of single-cell sequencing analysis shows the expression of FGFR1 in different cell populations. Data are presented as mean ± SD. **p < 0.01.

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Single Cell, Biomarker Discovery, Immunofluorescence, Staining, Expressing, Control, Sequencing

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: TGF-β induces endothelial cell profibrotic activation via the FGFR1/YAP1 axis. (A) Flow cytometry verifying >99% purity of isolated human umbilical vein endothelial cells (HUVECs) by CD31 expression. (B) Morphological changes of HUVECs treated with TGF-β (2.5, 7.5, 22.5 ng/ml): concentration-dependent transition from cobblestone to spindle-shaped, smooth muscle cell-like phenotype. Bar = 20 μm. (C) qPCR analysis of fibrotic markers (ACTA2, Vimentin) and YAP1 mRNA in TGF-β-stimulated HUVECs. Data are fold change vs. unstimulated control (set as 1). (D) Western blot showing TGF-β-induced upregulation of α-SMA, FGFR1, and YAP1 in HUVECs after 24-h treatment (0, 2.5, 7.5, 22.5 ng/ml). Data are fold change vs. unstimulated control (set as 1). (E–G) Semi-quantitative Western blot confirming TGF-β-induced upregulation of α-SMA (dose-dependent; (E) , FGFR1 (F) , and YAP1 (G) in HUVECs. n = 3. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significance.

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Activation Assay, Flow Cytometry, Isolation, Expressing, Concentration Assay, Control, Western Blot

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: PD173074 , an FGFR1 inhibitor, mitigates TGF-β-induced EndMT via targeting the FGFR1/YAP1 axis (A) Experimental protocol: HUVECs were seeded in 35 mm dishes, adhered for 12 h, then treated with 22.5 ng/ml TGF-β for 24 h to induce fibrosis, followed by intervention with 22.5 ng/ml TGF-β plus PD173074 (0, 10, 30, 90 nM). (B) Phase-contrast images showing PD173074 (30, 90 nM) reversed TGF-β-induced morphological transition from spindle-shaped to cobblestone-like phenotype. Bar = 20 μm (C) qPCR analysis of FGFR1, YAP1, and EndMT markers (ACTA2, Vimentin) mRNA in HUVECs under indicated conditions. Data normalized to GAPDH, presented as fold change vs. untreated control (set to 1). n = 3. (D) Western blot confirming PD173074 -induced downregulation of FGFR1, YAP1, and α-SMA, consistent with GAPDH-normalized semi-quantitative data (fold change vs. untreated control, set to 1). n = 4. Data are presented as mean +SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significance.

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Control, Western Blot

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: FGFR1 or YAP1 knockdown attenuates EndMT (A,B) Validation of FGFR1 knockdown efficiency in HUVECs at the protein (A) and mRNA (B) levels. (C) Western blot analysis demonstrated that TGF-β induces the upregulation of α-SMA, YAP1, and FGFR1 expression in shNC cells, while knockdown of FGFR1 inhibits this effect. (D) Morphological reversion of HUVECs from spindle-shaped (TGF-β-induced) to cobblestone-like after FGFR1 knockdown. Bar = 20 μm. (E) qPCR analysis showing TGF-β-induced upregulation of ACTA2, YAP1, ACTA2 and Vimentin in control cells, which was suppressed by FGFR1 knockdown. (F,G) Validation of YAP1 knockdown efficiency at the protein (F) and mRNA (G) levels. (H) qPCR analysis of ACTA2 and Vimentin mRNA confirming TGF-β-induced fibrosis and suppression by YAP1 knockdown. (I) Western blot analysis demonstrated that YAP1 knockdown significantly suppressed the TGF-β-induced upregulation of α-SMA and YAP1 expression. (J) Morphological reversion of HUVECs to cobblestone-like after YAP1 knockdown.​ Bar = 20 μm. All data are presented as mean +SD (n = 3). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significance. mRNA data were normalized to GAPDH or β-actin and expressed as fold change vs. scrambled control (set to 1).

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Knockdown, Biomarker Discovery, Western Blot, Expressing, Control

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: FGFR1 knockdown attenuates inflammation and endothelial dysfunction and reveals underlying mechanisms (A) qPCR analysis showed that FGFR1 knockdown reduced the mRNA levels of VCAM1, IL-6, and TNF-α under TGF-β stimulation. (B) Western blot analysis confirmed that FGFR1 knockdown decreased the protein expression of VCAM1 and IL-6 under TGF-β stimulation. (C) Under TGF-β stimulation, FGFR1 knockdown downregulated Ang2 mRNA expression compared with the shNC group. (D) FGFR1 knockdown decreased p-VE-cadherin protein expression under TGF-β stimulation relative to the shNC group. (E) Under TGF-β stimulation, FGFR1 knockdown reduced CCN2 mRNA expression compared with the shNC group. (F) Western blot analysis revealed that FGFR1 knockdown downregulated p-ERK and YAP1 protein levels under TGF-β stimulation relative to the shNC group. All data are presented as mean +SD (n = 3). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significance. mRNA data were normalized to GAPDH and expressed as fold change vs. scrambled control (set to 1).

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Knockdown, Western Blot, Expressing, Control

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: FGFR1 inhibitor PD173074 ameliorates UUO-induced renal atrophy, dysfunction, and tissue fibrosis. (A) Experimental timeline and gross renal morphology of sham-operated (control), UUO + vehicle (UUO), and UUO + PD173074 groups. (B) Left/right dry kidney weight ratio across experimental groups. (C) Serum creatinine levels in sham, UUO, and UUO + PD173074 mice. (D) Histological staining (H&E, Masson’s trichrome, Sirius Red): The UUO group showed typical fibrotic features (amorphous eosinophilic deposits, increased collagen, disrupted renal architecture) vs. controls (confirming successful modeling); PD173074 alleviated these changes. Bar = 50 μm and 20 μm, except Sirius Red staining (100 μm and 40 μm).

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Control, Staining

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: FGFR1 inhibitor PD173074 attenuates molecular markers of fibrosis induced by UUO. (A) Western blot and semi-quantification (GAPDH-normalized; fold change vs. control = 1): UUO upregulated α-smooth muscle actin (α-SMA) and Fibronectin in mouse renal tissues vs. sham. (B) Western blot and semi-quantification (GAPDH-normalized; fold change vs. UUO = 1): PD173074 reversed UUO-induced α-SMA and Fibronectin upregulation. (C,D) Immunofluorescence (FGFR1/vascular endothelial cadherin (VE-cadherin), YAP1/VE-cadherin; red/green): UUO-induced FGFR1 (C) and Yes-associated protein 1 (YAP1) (D) upregulation in renal endothelial cells was inhibited by PD173074 . Bar = 50 μm and 10 μm (E) Immunofluorescence: UUO-induced upregulation of extracellular matrix components (Fibronectin, Collagen I in renal tissues was downregulated by PD173074 . Bar = 100 μm and 20 μm. All data are presented as mean +SD (n ≥ 3). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significance.

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Western Blot, Control, Immunofluorescence

Journal: Frontiers in Pharmacology

Article Title: FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target

doi: 10.3389/fphar.2026.1766265

Figure Lengend Snippet: FGFR1 inhibition reduces inflammatory and endothelial permeability markers and suppresses p-ERK/YAP1 signaling in UUO and db/db mice. (A) qPCR analysis showed that FGFR1 inhibitor reduced VCAM1, IL-6, and TNF-α mRNA levels in UUO mice. (B,C) qPCR results confirmed that Ang2 and CCN2 mRNA levels were decreased in the UUO + FGFR1 inhibitor group. (D) Western blot analysis revealed reduced protein levels of VCAM1 and p-VE-cadherin in the UUO + FGFR1 inhibitor group. (E) p-ERK protein expression was decreased in the UUO + FGFR1 inhibitor group. (F) VCAM1 and p-ERK protein levels were elevated in 24 week db/db diabetic mice compared to db/m controls. (G) Masson staining showed marked renal interstitial fibrosis in 24 week db/db mice. (H) Immunofluorescence demonstrated increased FGFR1 and YAP1 expression in endothelial cells of 24 week db/db mice. All data are presented as mean +SD (n ≥ 3). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significance.

Article Snippet: In the subsequent treatment phase, to mimic the pathological microenvironment of persistent TGF-β stimulation as observed in vivo , cells were co-treated for 12 h with the FGFR1 inhibitor PD173074 (MedChemExpress, #HY-10321; 0, 10, 30, or 90 nM) in the continued presence of the corresponding TGF-β concentrations.

Techniques: Inhibition, Permeability, Western Blot, Expressing, Staining, Immunofluorescence