scholarly journals CDCP1 promotes compensatory renal growth by integrating Src and Met signaling

2021 ◽  
Vol 4 (4) ◽  
pp. e202000832
Author(s):  
Kentaro Kajiwara ◽  
Shotaro Yamano ◽  
Kazuhiro Aoki ◽  
Daisuke Okuzaki ◽  
Kunio Matsumoto ◽  
...  
Keyword(s):  
Compensatory Growth ◽  
Morphological Changes ◽  
Renal Tubules ◽  
Kidney Cells ◽  
Renal Growth ◽  
Compensatory Renal Growth ◽  
Stat3 Signaling ◽  
Cub Domain ◽  
Hepatocyte Growth ◽  
Canine Kidney

Compensatory growth of organs after loss of their mass and/or function is controlled by hepatocyte growth factor (HGF), but the underlying regulatory mechanisms remain elusive. Here, we show that CUB domain-containing protein 1 (CDCP1) promotes HGF-induced compensatory renal growth. Using canine kidney cells as a model of renal tubules, we found that HGF-induced temporal up-regulation of Src activity and its scaffold protein, CDCP1, and that the ablation of CDCP1 robustly abrogated HGF-induced phenotypic changes, such as morphological changes and cell growth/proliferation. Mechanistic analyses revealed that up-regulated CDCP1 recruits Src into lipid rafts to activate STAT3 associated with the HGF receptor Met, and activated STAT3 induces the expression of matrix metalloproteinases and mitogenic factors. After unilateral nephrectomy in mice, the Met-STAT3 signaling is transiently up-regulated in the renal tubules of the remaining kidney, whereas CDCP1 ablation attenuates regenerative signaling and significantly suppresses compensatory growth. These findings demonstrate that CDCP1 plays a crucial role in controlling compensatory renal growth by focally and temporally integrating Src and Met signaling.

scholarly journals CUB domain-containing protein 1 controls HGF responses by integrating Src and Met–STAT3 signaling

2019 ◽  
Author(s):  
Kentaro Kajiwara ◽  
Atsuya Sugihara ◽  
Kazuhiro Aoki ◽  
Daisuke Okuzaki ◽  
Kunio Matsumoto ◽  
...  
Keyword(s):  
Breast Cancer Cells ◽  
Renal Growth ◽  
Compensatory Renal Growth ◽  
Stat3 Signaling ◽  
Biological Responses ◽  
Organ Regeneration ◽  
Cub Domain ◽  
Hepatocyte Growth ◽  
Invasive Cell

AbstractHepatocyte growth factor (HGF) controls various biological responses, including morphogenesis, organ regeneration, and cancer invasion, by activating its receptor, Met. However, the mechanisms that precisely control diverse Met signaling remain unclear. Here, we identified CUB domain-containing protein 1 (CDCP1) as a crucial element of HGF signaling. In MDCK cysts, HGF induced Src activation via CDCP1 upregulation, and CDCP1 ablation abrogated HGF responses, i.e., extended invasive cell protrusions and promoted cell growth/proliferation. Mechanistically, CDCP1 upregulation promoted Src recruitment into lipid rafts to activate Met-associated STAT3. In breast cancer cells in which Met and CDCP1 were co-upregulated, CDCP1 knockdown suppressed HGF-induced cell invasion. Furthermore, in vivo analysis showed that CDCP1 ablation suppressed compensatory renal growth by attenuating Met–STAT3 signaling. These findings demonstrate that CDCP1 plays a crucial role in controlling HGF responses by integrating Src and Met-STAT3 signaling, and provide new insights into the regulatory mechanisms underlying the multifaceted functions of HGF.

scholarly journals Involvement of Focal Adhesion Kinase in Hepatocyte Growth Factor-induced Scatter of Madin-Darby Canine Kidney Cells

2000 ◽  
Vol 275 (11) ◽  
pp. 7474-7480 ◽  
Author(s):  
Jui-Fen Lai ◽  
Shu-Chen Kao ◽  
Si-Tse Jiang ◽  
Ming-Jer Tang ◽  
Po-Chao Chan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Hepatocyte Growth ◽  
Darby Canine Kidney ◽  
Canine Kidney

scholarly journals Compensatory Renal Growth after Unilateral Nephrectomy in the Ovine Fetus

2002 ◽  
Vol 13 (2) ◽  
pp. 406-410 ◽  
Author(s):  
Rebecca Douglas-Denton ◽  
Karen M. Moritz ◽  
John F. Bertram ◽  
E. Marelyn Wintour
Keyword(s):  
Compensatory Growth ◽  
Weight Ratio ◽  
In Utero ◽  
Unilateral Nephrectomy ◽  
Renal Growth ◽  
Compensatory Renal Growth ◽  
Glomerular Volume ◽  
Ovine Fetus ◽  
Wet Weight ◽  
The Right

ABSTRACT. Unilateral nephrectomy of the adult animal results in compensatory renal growth but does not involve formation of new nephrons. It is not clear whether compensatory growth can occur during the period of active nephrogenesis in utero and if so, whether more nephrons can be formed. Male ovine fetuses (n = 20) underwent unilateral nephrectomy (n = 10) or sham nephrectomy (n = 10) at 100 d of gestation (term, 150 d). After 27 to 34 d, ewes and fetuses were killed and the right kidney of each fetus was removed and weighed. The wet weight of the right kidney was greater in the unilaterally nephrectomized fetuses (16.3 ± 1.3 g compared with 12.2 ± 0.7 g; mean ± SEM, P < 0.05) as was the kidney to body weight ratio (5.2 ± 0.3 g/kg compared with 3.8 ± 0.2 g/kg; P < 0.001). Nephron number in the right kidney was estimated by an unbiased stereologic technique. There was a 45% increase in the number of nephrons in the kidneys from unilaterally nephrectomized animals compared with the kidneys from sham-operated animals (530,763 ± 37,136 nephrons in the unilaterally nephrectomized group compared with 365,672 ± 36,016 nephrons in the sham-operated group; P < 0.01). Mean glomerular volume was lower in the unilaterally nephrectomized group; however, total glomerular volume per kidney was not different between groups. This study demonstrates that there is a significant amount of compensatory growth and nephron endowment in a remaining kidney after unilateral nephrectomy during the period of active nephrogenesis in the sheep. This is the first time such events have been shown to occur in utero.

Hepatocyte growth factor upregulates α2β1 integrin in Madin-Darby canine kidney cells: Implications in tubulogenesis

2002 ◽  
Vol 9 (3) ◽  
pp. 261-272 ◽  
Author(s):  
Sue-Jean Chiu ◽  
Si-Tse Jiang ◽  
Yang-Kao Wang ◽  
Ming-Jer Tang
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Hepatocyte Growth ◽  
Α2β1 Integrin ◽  
Darby Canine Kidney ◽  
Canine Kidney

Hepatocyte growth factor inhibits intrinsic antibacterial activity of Madin-Darby canine kidney cells

2004 ◽  
Vol 6 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Brian K. Wade ◽  
Jason K. Burrus ◽  
Daniel F. Balkovetz
Keyword(s):  
Antibacterial Activity ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Hepatocyte Growth ◽  
Darby Canine Kidney ◽  
Canine Kidney

scholarly journals JAM4 enhances hepatocyte growth factor-mediated branching and scattering of Madin-Darby canine kidney cells

2004 ◽  
Vol 9 (9) ◽  
pp. 811-819 ◽  
Author(s):  
Hiroki Mori ◽  
Susumu Hirabayashi ◽  
Madoka Shirasawa ◽  
Haruhiko Sugimura ◽  
Yutaka Hata
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Hepatocyte Growth ◽  
Darby Canine Kidney ◽  
Canine Kidney

Evaluation of Na+ Active Transport and Morphological Changes for Bioartificial Renal Tubule Cell Device Using Madin-Darby Canine Kidney Cells

2002 ◽  
Vol 8 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Yuji Fujita ◽  
Takatosi Kakuta ◽  
Manabu Asano ◽  
Johbu Itoh ◽  
Kou Sakabe ◽  
...  
Keyword(s):  
Active Transport ◽  
Renal Tubule ◽  
Morphological Changes ◽  
Kidney Cells ◽  
Tubule Cell ◽  
Madin Darby Canine Kidney ◽  
Renal Tubule Cell ◽  
Darby Canine Kidney ◽  
Canine Kidney

Hepatocyte Growth Factor Upregulates α2β1 Integrin in Madin-Darby Canine Kidney Cells: Implications in Tubulogenesis

2002 ◽  
Vol 9 (3) ◽  
pp. 261-272 ◽  
Author(s):  
Sue-Jean Chiu ◽  
Si-Tse Jiang ◽  
Yang-Kao Wang ◽  
Ming-Jer Tang
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Beta 1 Integrin ◽  
Hepatocyte Growth ◽  
Darby Canine Kidney ◽  
Canine Kidney
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